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Biomedical subjects

C Kaufmann

Publications and source records attributed to C Kaufmann.

At least 55 records · Page 3Linked to original sources

Hypothermic coagulopathy in trauma: effect of varying levels of hypothermia on enzyme speed, platelet function, and fibrinolytic activity.

BACKGROUND: The coagulopathy noted in hypothermic trauma patients has been variously theorized to be caused by either enzyme inhibition, platelet alteration, or fibrinolytic processes, but no study has examined the possibility that all three processes may simultaneously contribute to coagulopathy, but are perhaps triggered at different levels of hypothermia. The purpose of this study was to determine whether, at clinically common levels of hypothermia (33.0-36.9 degrees C), there are specific temperature levels at which coagulopathic alterations are seen in each of these processes. METHODS: Of 232 consecutive adult trauma patients presenting to a Level I trauma center, 112 patients met the inclusion criteria of an Injury Severity Score of 9 or greater and time since injury of less than 2 hours. Of the included patients, 40 were normothermic and 72 were hypothermic (> or =37 degrees C, n = 40; 36.9-36 degrees C, n = 29; 35.9-35 degrees C, n = 20; 34.9-34 degrees C, n = 16; 33.9-33 degrees C, n = 7). Included patients were prospectively studied with thrombelastography adjusted to core body temperature. Additionally, PT, aPTT, platelets, CO2, hemoglobin, hematocrit, and Injury Severity Score were measured. RESULTS: Analysis by multivariate analysis of variance of the relationship between coagulation and temperature demonstrated that in hypothermic trauma patients, 34 degrees C was the critical point at which enzyme activity slowed significantly (p < 0.0001), and at which significant alteration in platelet activity was seen (p < 0.001). Fibrinolysis was not significantly affected at any of the measured temperatures (p > 0.25). CONCLUSIONS: Patients whose temperature was > or =34.0 degrees C actually demonstrated a significant hypercoagulability. Enzyme activity slowing and decreased platelet function individually contributed to hypothermic coagulopathy in patients with core temperatures below 34.0 degrees C. All the coagulation measures affected are part of the polymerization process of platelets and fibrin, and this process may be the mechanism by which the alteration in coagulation occurs.

Adolescent↗

Penetrating cardiac injuries: a population-based study.

BACKGROUND: Wide variances exist in reports of survival rates after penetrating cardiac injuries because most are hospital-based reports and thus are affected by the local trauma system. The objective of this study was to report population-based, as well as hospital-based, survival rates after penetrating cardiac injury. METHODS: Retrospective cohort analysis was performed during a 7-year period of 20,181 consecutive trauma admissions to a regional Level I trauma center and 6,492 medical examiner's reports. A meta-analysis was performed comparing survival rates with available population-based reports. RESULTS: There were 212 penetrating cardiac injuries identified, for an incidence of approximately 1 per 100,000 man years and 1 per 210 admissions. The overall survival rate was 19.3% (41 of 212) for the population studied, with survival rates of 9.7% (12 of 123) for gunshot wounds and 32.6% (29 of 89) for stab wounds. Ninety-six of the 212 patients were transported to the trauma center for treatment, resulting in an overall hospital survival rate of 42.7% (41 of 96), with a hospital survival rate of 29.3% (12 of 41) for gunshot wounds and 52.7% (29 of 55) for stab wounds. CONCLUSION: Review of population-based studies indicates that there has been only a minor improvement in the survival rates for the treatment of penetrating cardiac injuries.

Academic Medical Centers↗

Making the grade: update on report card initiatives for 1997.

Report cards for healthcare services are increasingly in the news, offering the hope that objective information on the quality of health plan and providers services will eventually enable purchasers and consumers to make selections based on true value. Following is a series of five brief articles that review ongoing report card initiatives in private and public sectors of the behavioral healthcare system. The first four articles review actual report cards designed to hold organizations--particularly managed care--accountable for the quality of their services. The last article reviews research on performance measurement across all segments of the behavioral healthcare industry.

Data Collection↗

[Measurement of stress parameters in farm animals using active telemetry].

We investigated the effect of an acute stressor on body temperature and heart rate in cows. Both parameters were recorded by active telemetry. For the experiments, five cyclic Brown Swiss cows were used, each of them exposed to an acute stressor during estrus and the luteal phase of the cycle. The stressor consisted in restraining the cows in a crush for hoof treatments. During the 2-hour stress period and for additional 6 hours, body temperature and heart rate were measured every 10 minutes. Control animals remained in their accustomed environment during the whole experiment of 8 hours. The course of body temperature and heart rate was clearly influenced by the stressor. While heart rate was maximal already at the beginning of the stress period, the body temperature showed highest values only one hour after stress and then continuously decreased. Changes in body temperature and heart rate under stress differed significantly from the values of control animals. Both parameters are reliable indicators of stress in the bovine species. The transmitters used in this investigation allowed us to register exact data without manipulation of the animal, which could possibly falsify the results. This advantage as well as the functional longevity of the transmitters (ca. 6 months) make active telemetry a useful tool for stress research in farm animals.

Animals↗

Uniform prehospital data elements and definitions: a report from the uniform prehospital emergency medical services data conference.

One of the district and universal aspects of emergency medical service (EMS) is the belief that before its implementation many people were dying or being killed by ill-equipped, poorly trained "hearse drivers" and that this tragic state of affairs has been rectified by the advances in the prehospital phase of care. Except for cases of nontraumatic, out-of-hospital cardiac arrest there is almost no convincing scientific evidence to prove that prehospital care has had an impact on morbidity or mortality. At the very foundation of this problem is the lack of a set of broad-based, well-conceived, accurate, reliable, uniform EMS data. Many attempts have been made to develop a uniform EMS data set, but without a national consensus these have not achieved wide distribution. In 1992, with the assistance of the National Highway Traffic Safety Administration, the national consensus process began with a series of meetings involving many EMS agencies and organizations. This culminated in August 1994 with the development of an 81-item uniform EMS data set. We detail the prior attempts at data set development and outline the process leading to the this uniform, national EMS data set.

Data Collection↗

Pharmacokinetics of Ara-CMP-Stearate (YNK01): phase I study of the oral Ara-C derivative.

Ara-CMP-Stearate (1-beta-D-arabinofuranosylcytosine-5'-stearylphosphate, YNK 01, Fosteabine) is the orally applicable prodrug of cytosine-arabinoside (Ara-C). During a phase I study in patients with advanced low-grade non-Hodgkin lymphomas or acute myeloid leukemia, the pharmacokinetic parameters of Ara-CMP-Stearate (kindly provided by ASTA Medica, Frankfurt, Germany) were determined by HPLC analysis. Seventy-two hours after a first starting dose which served for the determination of baseline pharmacokinetic parameters, Ara-CMP-Stearate was administered over 14 days by daily oral application. Ara-CMP-Stearate was started at a dose of 100 mg/day and was escalated in subsequent patients to 200 mg/day and 300 mg/day. Plasma and urine concentrations of Ara-CMP-Stearate, Ara-C and Ara-U were measured during the initial treatment phase and within 72 h after the end of the 14-day treatment cycle. So far six patients have been treated with 100 mg/day, three with 200 mg/day and another six with 300 mg/day. One patient was treated consecutively with 100 mg, 300 mg and 600 mg. Fitting the results of the plasma concentration measurements of Ara-CMP-Stearate to a one-compartment model, the following pharmacokinetic parameters were obtained (average and variation coefficient VC). Ara-CMP-Stearate dose-independent parameters: lag time = 1.04 h (0.57); tmax = 5.72 h (0.30); t1/2 = 9.4 h (0.36). Dose-dependent parameters: at 100 mg: AUC = 1099 ng/h/ml (0.31); concentration(max) = 53.8 ng/ml (0.28); at 200 mg: AUC = 2753 ng/h/ml (0.32); concentration(max) = 154.8 ng/ml (0.46); at 300 mg: AUC = 2940 ng/h/ml (0.66); concentration(max) = 160.0 ng/ml (0.59). The long lag time and late tmax can be explained by resorption in the distal part of the small intestine. No Ara-CMP-Stearate was detected in urine samples (limit of detection = 500 pg/ml). Pharmacokinetic parameters of Ara-C following Ara-CMP-Stearate application showed the following characteristics: t1/2 = 24.3 h (0.39); AUC (100 mg) = 262 ng/h/ml (0.93); AUC (200 mg) = 502 ng/h/ml (0.87); AUC (300 mg) = 898 ng/h/ml (1.07). Since Ara-CMP-Stearate causes intravascular hemolysis after intravenous administration, it was not possible to determine its bioavailability by comparing the AUC after oral and i.v. application. Instead, the renal elimination of Ara-U, as the main metabolite of Ara-C was measured during the first 72-h period and after the last application.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗

[Comparative analysis of mental health treatment of various groups of competitive athletes].

1) There is sense and necessity of psychohygiene in sports. This could be stated with 3 compared groups, namely: a national team, a team of handicapped, a team of juveniles. 2) We have used a complex program with integrated autogenic training (this however, not in an isolated way). Earlier experiences (of last author) over many years and hundreds of sportives were integrated in our evaluation. 3) Its to our knowledge the first time in world literature that effectiveness of psychohygiene within sports could be proved with statistical significance using world cup points within comparable groups. 4) Only possible can be possible, and psychohygiene will help to optimate this goal but not overrun it. This is main differentiation against doping. The human and the humanity is the main goal and not the so-called "necessities" of sport dictatorship. Its a good sign that several of our candidates told us that our psychohygienic program has reached over their period of sports activities into their "normal" lives.

Adaptation, Psychological↗

[Outcome-oriented Barolin Neurorehabilitation Scale: 476 cases over 6 years--multi-nodal statistical correlation of neurorehabilitation groups in diagnosis, prognosis and outcome].

This evaluation documents practicability and scientific value of the scale, since many years developed in our institute and in use there. Patients with left hemispheric lesions suffer from stronger disturbances of eating than others. Systematic neurological rehabilitations leads to a marked increased unnecessity of catheterism and by that to a marked better social integration. Associate depression (after Barolin) is a main source of rehabilitation hospitalism (as called by Barolin). Multiple sclerosis and Morbus Parkinson give better outcomes than cerebro-vascular patients. A new finding that also proofs to be neurophysiologically interesting is that higher agedness is mostly a non-limiting factor for rehabilitation, as far as not lesser endavours produce a self fulfilling prophecy. However a slight limitation in higher age groups is to be found in the patients with lesions on the dominant hemisphere, whereas lesions on the subdominant hemisphere produce no limitation to rehabilitation at all by higher age.

Activities of Daily Living↗

Falsely negative 99mTc-antigranulocyte immunoscintigraphy and positive 99mTc-HMPAO-labelled leukocyte scan in active Crohn's disease. Possible effects of immunosuppressive therapy?

A 19-year-old woman with active Crohn's disease under immunosuppressive therapy underwent scintigraphy with 99mTc-anti-NCA-95 antigranulocyte antibodies in order to determine the extent of inflammation. It turned out to be falsely negative whereas a 99mTc-HMPAO-labelled leukocyte scan revealed a marked terminal ileitis and pancolitis. It is assumed that immunosuppressive therapy was the main reason for the falsely negative antibody scan, possibly affecting the red bone marrow where most of the antibodies bind to granulocytes. Peripheral leukocytes labelled in vitro do not seem to be subject to these hypothetical effects on red bone marrow.

Adult↗

Amino acid residues lining the chloride channel of the cystic fibrosis transmembrane conductance regulator.

The cystic fibrosis transmembrane conductance regulator forms a chloride channel that is regulated by phosphorylation and intracellular ATP levels. The structure of the channel-forming domains is undetermined. To identify the residues lining this channel we substituted cysteine, one at a time, for 9 consecutive residues (91-99) in the M1 membrane-spanning segment. The cysteine substitution mutants were expressed in Xenopus oocytes. We determined the accessibility of the engineered cysteine to charged, sulfhydryl-specific methanethiosulfonate reagents added extracellularly. We assume that, among residues in membrane-spanning segments, only those lining the channel will be accessible to react with these hydrophilic reagents and that such a reaction would irreversibly alter conduction through the channel. Only the cysteines substituted for Gly-91, Lys-95, and Gln-98 were accessible to the reagents. We conclude that these residues are in the channel lining. The periodicity of these residues is consistent with an alpha-helical secondary structure.

Amino Acid Sequence↗

Identification of acetylcholine receptor channel-lining residues in the entire M2 segment of the alpha subunit.

Each residue in and flanking the M2 membrane-spanning segment of the alpha subunit, from Glu-241 to Glu-262, was mutated to cysteine, and the mutant subunits were expressed together with wild-type beta, gamma, and delta subunits in Xenopus oocytes. Cysteines substituted for Glu-262, Leu-258, Val-255, Ser-252, Leu-251, Leu-250, Ser-248, Leu-245, Thr-244, and Glu-241 reacted with the positively charged, hydrophilic, sulfhydryl-specific reagent methanethiosulfonate ethylammonium (MTSEA), added extracellularly. These 10 residues, therefore, are exposed in the channel lumen. The pattern of exposure is compatible with an alpha helix, interrupted by an extended structure from Leu-250 to Ser-252. Acetylcholine caused subtle changes in the accessibilities of some of the engineered cysteines. Since all 10 residues are accessible to MTSEA in the closed state of the channel, the channel gate is at least as cytoplasmic as Glu-241, the most cytoplasmic of the residues tested.

Acetylcholine↗

Negatively charged amino acid residues in the nicotinic receptor delta subunit that contribute to the binding of acetylcholine.

In nicotinic receptors, the binding sites for acetylcholine are likely to contain negatively charged amino acid side chains that interact with the positively charged quaternary ammonium group of acetylcholine and of other potent agonists. We previously found that a 61-residue segment of the delta subunit contains aspartate or glutamate residues within 1 nm of cysteines in the acetylcholine binding site on the alpha subunit. We have now mutated, one at a time, the 12 aspartates and glutamates in this segment of the mouse muscle delta subunit and have expressed the mutant receptors in Xenopus oocytes. Both the concentration of acetylcholine eliciting half-maximal current (Kapp) and the Ki for the inhibition by acetylcholine of alpha-bungarotoxin binding were increased 100-fold by the mutation of delta Asp180 to Asn and 10-fold by the mutation of delta Glu189 to Gln. These two residues, and their homologs in the gamma and epsilon subunits, are likely to contribute to the acetylcholine binding sites.

Acetylcholine↗

Epidemiology of the post-polio syndrome.

A late-onset syndrome, consisting of muscle weakness, muscle pain, and unaccustomed fatigue, has been reported with increasing frequency among former poliomyelitis patients. A population-based cohort of poliomyelitis patients from Allegheny County, Pennsylvania, was traced and surveyed to estimate the prevalence and incidence and to identify determinants of the post-polio syndrome. A questionnaire validated in clinical examinations of 40 cohort members was used in the survey. The prevalence of the post-polio syndrome was 28.5% of all paralytic cases (95% confidence interval 24.4-32.6). The risk of post-polio syndrome was significantly higher among patients who sustained substantial permanent impairment after polio and among females. The incidence did not vary with age at acute onset, acute severity, or level of physical activity after recovery. The strongest determinant of post-polio syndrome onset was the length of the interval following the acute illness, with incidence peaking at 30-34 years. Of all cases of post-polio syndrome, 79% reported no major change in impairment status since onset. This study demonstrates that poliomyelitis patients are not equally susceptible to post-polio syndrome within the interval of 30-40 years after the original illness. For syndrome cases, the onset was associated with new neuromuscular symptoms and functional changes but not with major new impairment.

Acute Disease↗

[Concomitant depression and its treatment].

Accompanying depression is especially common in elderly, chronically ill patients and rehabilitation patients, where a physical illness and/or disablement is accompanied by depression. Treatment should always be focussed in a "polypragmatic" manner on both physical or psychic symptoms. In particular psychotherapy (see article by Barolin), pharmacotherapy (referred to in this article) and physiotherapy (described further in other literature) are of importance here. Advantage is to be taken of the polar dimensions of different types of antidepressant drugs, namely the increase in drive or sedating effects. However, the increased rate of side effects from some drugs among elderly patients is not to be ignored. Taking the above into consideration, the new antidepressant, Fluctine (Fluoxetine), has proved to be effective among our randomly selected patients. This is on account of its relatively fast onset of action, minimal side effects and its slight increase in drive. The group of non-responders (one third of the patients) showed no decrease in depressive symptoms when other antidepressants were substituted. As expected those patients suffering organic-brain illness responded worse and represent a large percentage of the non-responders. These data prove the results of previous findings that patients with organic-brain illness generally respond worse to antidepressant medication. Thus Fluctine can be recommended for elderly patients with accompanying depression.

Adaptation, Psychological↗

Measuring the inflation of the lod score due to its maximization over model parameter values in human linkage analysis.

A computer-simulation method is presented for determining and correcting for the effect of maximizing the lod score over disease definitions, penetrance values, and perhaps other model parameters. The method consists of simulating the complete analysis using marker genotypes randomly generated under the assumption of free recombination. It is applicable as a "post-treatment" to linkage analyses of any trait with an uncertain mode of inheritance and/or disease definition. When the method is applied to a linkage analysis of schizophrenia versus chromosome 5 markers, we find that, in this specific case, the P-value associated with a maximum lod score of 3 is equal to 0.0003. We also find that a lod score of 3.0 should be "deflated" by approximately 0.3 to 1 units, and, by tentative extrapolation, the observed lod score of 6.5 should be "deflated" by 0.7 to 1.5 units.

Chromosomes, Human, Pair 5↗