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Biomedical subjects

C Kaufmann

Publications and source records attributed to C Kaufmann.

At least 19 recordsLinked to original sources

Ultrasound imaging for external-beam prostate treatment setup and dosimetric verification.

Ultrasound (US) image-guided patient positional verification was performed daily on four prostate cancer patients using the BAT system (NOMOS Corporation, CA). The BAT system has shown that the prostate can shift by as much as 1 cm from its intended position in any direction. Furthermore, the daily shifts measured by the BAT system were included into the treatment planning system to assess changes in prostate dose coverage. Dose volume histograms were used to compare the dosimetry between the ideal patient set-up situation (prostate always positioned correctly) and that taking all patient daily shifts into consideration. Daily patient shifts on the order of magnitudes measured, can significantly and adversely affect dosimetric coverage, therefore an US-based patient positioning system is required for improving the therapeutic ratio.

Humans↗

Frequency dependence and gender effects in visual cortical regions involved in temporal frequency dependent pattern processing.

Neural response to flickering stimuli has been shown to be frequency dependent in the primary visual cortex. Controversial gender differences in blood oxygen level dependent (BOLD) amplitude upon 6 and 8 Hz visual stimulation have been reported. In order to analyze frequency and gender effects in early visual processing we employed a passive graded task paradigm with a dartboard stimulus combining eight temporal frequencies from 0 to 22 Hz in one run. Activation maps were calculated within Statistical Parametric Mapping, and BOLD amplitudes were estimated for each frequency within the striate and extrastriate visual cortex. The BOLD amplitude was found to steadily rise up to 8 Hz in BA 17 and 18 with an activation plateau at higher frequencies. In addition, we observed a laterality effect in the striate cortex with higher BOLD contrasts in the right hemisphere in men and in women. BOLD response rises similarly in men and women up to 8 Hz but with lower amplitudes in women at 4, 8, and 12 Hz (30% lower). No frequency effect above 1 Hz was found in the extrastriate visual cortex. There was also a regional specific gender difference. Men activated more in the right lingual gyrus (BA 18) and the right cerebellum compared with women, whereas women showed more activation in the right inferior temporal gyrus (BA 17). The study indicates that frequency dependent processing at the cortical level is limited to the striate cortex and may be associated with a more global information processing (right hemisphere dominance), particularly in men. The finding of significantly lower BOLD amplitudes in women despite previously shown larger VEP (visual evoked potential) amplitudes might suggest gender differences in cerebral hemodynamics (baseline rCBV, rCBF, or neurovascular coupling). The regional distinction points at additional differences in psychological processing even when using a simple visual stimulus.

Adult↗

Ontogeny of neurohormonal peptides, serotonin, and nitric oxide synthase in the gastrointestinal neuroendocrine system of the axolotl (Ambystoma mexicanum): an immunohistochemical analysis.

The ontogeny of the neurohormonal peptides vasoactive intestinal polypeptide (VIP), neurotensin (NT), substance P (SP), calcitonin gene-related peptide (CGRP), gastrin/cholecystokinin (GAS/CCK), and somatostatin (SOM) as well as serotonin (SER) and nitric oxide synthase (NOS) was investigated in the gastrointestinal tract of the urodele Ambystoma mexicanum, the axolotl, using immunohistochemical techniques. The first regulatory substances to appear were SP, SOM, and SER that could be immunohistochemically detected up from stage 1. At early stage 2, VIP immunoreactivity was observed infrequently in enteric nerve fibers. With the onset of external feeding at late stage 2, SP-immunoreactive (IR) and SER-IR endocrine cells and VIP-IR nerve fibers were present throughout the gastrointestinal tract. Furthermore, in the small intestine NT-IR and GAS/CCK-IR endocrine cells appeared. At stage 3, SER immunoreactivity was observed not only in endocrine cells but also in nerve fibers. CGRP-IR and SP-IR nerve fibers were detectable at stage 4 and stage 5, respectively. From stage 5 on, a minority of the CGRP immunoreactivity occurred in SP-IR nerve fibers. NOS immunoreactivity did not appear before stage 6 when it was found infrequently in nerve fibers. Thus, several phases of development can be distinguished: (1) at the yolk sac stages only few regulatory substances are present. (2) At the onset of external feeding, all endocrine cell types investigated were readily detectable. Thus, the onset of external feeding seems to trigger the development of the gastrointestinal endocrine system. (3) The endocrine cells are first found in the proximal part of the gastrointestinal tract and later in higher numbers in the distal parts. (4) The dually distributed neurohormonal peptides and SER first appear in endocrine cells and later additionally in nerve fibers. Thus, the nerve fibers likely set up the fine regulation of gastrointestinal blood flow and motility.

Ambystoma↗

Gray matter-changes and correlates of disease severity in schizophrenia: a statistical parametric mapping study.

Voxel-based morphometry has recently been used successfully to detect gray matter volume reductions in schizophrenic patients. The aim of the present study was to confirm the findings on gray-matter changes and to complement these by applying the methodology to CSF-differences. Also, we wanted to determine whether a correlation exists between a clinically defined parameter of disease severity and brain morphology in schizophrenic patients. We investigated 48 schizophrenic patients and compared them with 48 strictly age- and sex-matched controls. High-resolution whole-brain MR-images were segmented and analyzed using SPM99. In a further analysis, the covariate effect of the global assessment of functioning-score (GAF) was calculated. Main findings were (i) left-dominant frontal, temporal, and insular GM-reductions and (ii) GM-increases in schizophrenic patients in the right basal ganglia and bilaterally in the superior cerebellum; (iii) CSF-space increases in patients complementary to some GM-reductions; (iv) a correlation between the GAF-score and local GM-volume in the left inferior frontal and inferior parietal lobe of schizophrenic patients. This study confirms and extends some earlier findings on GM-reduction and detected distinct GM-increases in schizophrenic patients. These changes were corroborated by complementary CSF-increases. Most importantly, a correlation could be established between two particular gray matter-regions and the overall disease severity, with more severely ill patients displaying a local GM-deficit. These findings may be of potentially large importance for both the future interpretation and design of neuroimaging studies in schizophrenia and the further elucidation of possible pathophysiological processes occurring in this disease.

Adult↗

Aerosols produced by high-speed cutters in cervical spine surgery: extent of environmental contamination.

High-speed cutters are used in the surgery of the cervical spine. Such high-speed devices can produce an aerosol cloud. As a patient can be a reservoir for pathogens, with aerosol-borne paths of transmission, such an aerosol has to be seen as a potential risk of infection for health care professionals present during the surgery and for patients if micro-organisms are transferred through the medical personnel. The study was performed in order to measure the extension of environmental and body contamination through contaminated aerosols produced by a high-speed cutter. Three laminectomies (C4-C6) were performed on an intact human cadaver with a high-speed 0.6-mm ball cutter. A complete surgical setup was arranged, including surgical draping and a barrier drape to the anesthesiologist's workplace. Body and environmental contamination was detected by the use of surveillance cultures. The irrigation solution was artificially contaminated with Staphylococcus aureus ATCC 12600. Following the surgery, staphylococci were detected in the operating room at an extension of 5x7 m. Everybody showed extensive face and body contamination with Staphylococcus aureus. The study showed that the use of high-speed cutters in surgery of the cervical spine produces an aerosol cloud that is spread over the whole surgical room and contaminates the theater and all personnel present. Such aerosols can be contaminated with pathogens if the patient was infected or colonized. Therefore, sufficient protective measures have to be recommended for everyone present in the operating room during such surgeries. In addition, efficient disinfection of the room and all mobile equipment is necessary after each surgery involving high-speed cutting devices.

Aerosols↗

Effect of hydroxyethyl starch on coagulopathy in a swine model of hemorrhagic shock resuscitation.

BACKGROUND: Hydroxyethyl starch (HES) has a known dose-dependant effect on coagulopathy. The purpose of this study was to determine the effect of HES on coagulopathy after a period of hemorrhagic shock. METHODS: Anesthetized swine underwent a 15-minute, 40% blood volume hemorrhage (28 mL/kg) and a 1-hour shock period, followed by resuscitation with sham resuscitation (group I); 6% HES, 15 mL/kg (group II); 5% albumin, 15 mL/kg (group III); lactated Ringer's solution, 39 mL/kg, and 6% HES, 15 mL/kg (group IV); and lactated Ringer's solution, 39 mL/kg, and 5% albumin, 15 mL/kg (group V). Coagulation function was measured by bleeding time, prothrombin time, partial thromboplastin time, fibrinogen, platelet count, and thromboelastography. RESULTS: Platelet counts decreased significantly (p < 0.05) in all resuscitation groups except the sham resuscitation group. A significant decrease in platelets, fibrinogen levels, and maximum amplitude on thromboelastography was related to a dilutional effect of the fluid given and not a result of HES at the dose tested. CONCLUSION: The linear dose-related coagulopathic effects of HES when given at moderate doses does not seem to be worsened by prolonged periods of hemorrhagic shock. The coagulopathy seen during resuscitation from hemorrhagic shock seems to be a dilutional effect.

Analysis of Variance↗

Trauma training: virtual reality applications.

Training medics, medical students, nurses, and residents to perform trauma care skills presents many obstacles. These include: emergent nature of the procedures, instructor time, availability of clinical material, and anatomic knowledge. Virtual Reality simulators address each of these obstacles. The National Capital Area Medical Simulation Center is a unique national asset that not only uses state-of-the-art simulators to teach trauma care skills to medical students and others, but adapts existing technology and develops new simulations to teach these skills. Most standard trauma training is performed on either mannequins or anesthetized animals and requires the constant presence of an instructor. VR applications can be stand-alone devices that have built-in scenarios and multiple patients to increase variation and/or level of technical expertise required to successfully complete the required steps of the trauma procedure. Commercial VR simulators to teach trauma skills include: CathSim Intravenous Simulator (HT Medical), UltraSim Ultrasound Simulator (MedSim), Limb Trauma Simulator (Musculographics/BDI), and the Human Patient Simulator (MedSim). Additionally, we have developed two additional simulators based on the HT CathSim; these are the pericardiocentesis simulator and the diagnostic peritoneal lavage simulator. Future applications include virtual environment triage simulation and surgical airway simulators.

Clinical Competence↗

A computer-based simulator for diagnostic peritoneal lavage.

Diagnostic peritoneal lavage (DPL) is an emergency diagnostic procedure performed when intra-abdominal bleeding secondary to trauma is suspected. This procedure is part of the surgical skills section of the Advanced Trauma Life Support course. DPL is traditionally taught using anesthetized animals or cadavers. For reasons described below, these alternatives are not ideal. We have developed a computer-based diagnostic peritoneal lavage simulator. Our system addresses the shortcomings of the traditional method. We have used our system to teach ATLS. Preliminary results suggests that our system is effective.

Abdominal Injuries↗

[Amiodarone-induced thyrotoxicosis].

Amiodarone is the most important drug in the treatment of ventricular arrhythmias and is widely used for atrial fibrillation. Thyrotoxicosis, a classical side effect, was thought to be iodine induced, but recent evidence suggests that other mechanisms play an important role (toxic effect on thyreocytes, immunological effects). Thyrotoxicosis due to amiodarone is difficult to treat and is further complicated by the pro-arrhythmic potential of thyrotoxicosis and the fading antiarrhythmic effect after amiodarone withdrawal. The mechanism, diagnosis and therapy of amiodarone-induced thyrotoxicosis are discussed in the light of the available literature.

Amiodarone↗

The cytoplasmic domain of the alpha1 integrin subunit influences stress fiber formation via the conserved GFFKR motif.

Integrins are heterodimeric transmembrane proteins that mediate substrate adhesion and migration but also the bidirectional transfer of information across the plasma membrane via their cytoplasmic domains. We addressed the question of whether the very short cytoplasmic tail of the alpha1 integrin subunit of alpha1beta1 integrin is required for alpha1beta1-specific adhesion, spreading, and migration. For this purpose we transfected the alpha1 integrin subunit and two cytoplasmically truncated alpha1 subunits into Chinese hamster ovary (CHO) cells. Elimination of the entire cytoplasmic domain of the alpha1 subunit does not affect adhesion but leads to inhibition of spreading and stress fiber formation. The defect in spreading could not be rescued by lysophosphatidic acid, which has been reported to stimulate actin stress fiber formation via Rho. Additionally, deletion of the entire cytoplasmic domain of the alpha1 subunit abolishes migration toward alpha1beta1-specific substrates. Migration and stress fiber formation are similar in CHO-alpha1 cells and CHO cells carrying an alpha1 subunit still containing the conserved GFFKR motif. So, the GFFKR motif of the alpha1 subunit is essential and sufficient for these processes.

Actins↗

Induced hypothermia during emergency department thoracotomy: an animal model.

BACKGROUND: Induced hypothermia is used clinically to prevent ischemic injury during elective procedures. We present an animal model of asanguinous hypothermic (10 degrees C) circulatory arrest, induced through a left anterior lateral thoracotomy after exsanguinating uncontrolled hemorrhage. METHODS: Through a left anterior thoracotomy, 26 swine (45-70 kg) sustained a laceration of the descending thoracic aorta, producing exsanguinating uncontrolled hemorrhage. After 5 minutes of severe hypotension (systolic BP <20 mm Hg), a 22 French Foley catheter was directed cephalad through the enlarged aortic wound. A solution (containing 42.5 mmol/L K+ and precooled to 1 degrees C) was infused to arrest/preserve the heart and brain. A second 24 French Foley catheter was then directed caudally through the same wound. The right atrium was opened to drain the venous system. The animal was cooled with a cardiopulmonary bypass pump (>5L/min) through the Foley catheters. Once 10 degree C was reached, a cannula was placed to the aortic root and the aortic laceration repaired. The animal was maintained at 10 degree C for a total of 90 minutes. Before the rewarming process, the circulation was rinsed with a solution containing normal levels of electrolytes followed by infusion of whole blood. Rewarming was performed by maintaining a 10-degree gradient on the heat exchanger. The first 16 animals were used in nonsurvival experiments to develop the technique and to record dural temperatures and electroencephalogram tracings. The last 10 animals were used to determine long-term survival and neurologic outcome. Group I: seven animals were kept at < 10 degrees C with flows less than 2L/min. Group II: three animals underwent 20, 30, and 40 minutes of no flow once they were cooled to 10 degrees C. After 6 weeks of survival and neurologic examinations, the brains were fixed for histologic evaluations. RESULTS: The average time to cool the head to 18 degrees C and 10 degrees C was 6 minutes and 12 minutes, respectively. The hematocrit fell below 2% by the end of the cooling period. A total of 7 of the 10 animals from the long-term study survived. Group I: five of seven animals survived. Four of the survivors had no appreciable neurologic deficits, were fully functional at 6 weeks, and had no evidence of histologic injury. One of the five survivors in this group had moderate neurologic disability. Of the two animals that died, one died from air embolism from the i.v. line. The second death was in an animal for which maximal cooling to 2.7 degrees C was attempted. Group II: The first two animals that had "no flow" for 20 and 30 minutes were fully functional and had normal neurologic examinations. However, the second animal was found to have brain injury on histologic examination. The last animal in this group died of accidental extubation during recovery. CONCLUSION: Induction of hypothermic arrest through the chest after exsanguination is possible. The further development of this technique may provide an extended state of "suspended animation" to allow for repairs of hemorrhaging injuries in trauma patients who require emergency department thoracotomy.

Animals↗

Lactated ringer's solution and hetastarch but not plasma resuscitation after rat hemorrhagic shock is associated with immediate lung apoptosis by the up-regulation of the Bax protein.

BACKGROUND: We previously demonstrated that the type of resuscitation fluid used in hemorrhagic shock affects apoptosis. Unlike crystalloid, whole blood seems to attenuate programmed cell death. The purpose of this study was to determine whether the acellular components of whole blood (plasma, albumin) attenuated apoptosis and to determine whether this process involved the Bax protein pathway. METHODS: Rats were hemorrhaged 27.5 mL/kg, kept in hypovolemic shock for 75 minutes, then resuscitated over 1 hour (n = 44). Control animals underwent anesthesia only (sham, n = 7). Treatment animals were bled then randomly assigned to the following resuscitation groups: no resuscitation (n = 6), whole blood (n = 6), plasma (n = 6), 5% human albumin (n = 6), 6% hetastarch (n = 7), and lactated Ringer's solution (LR, n = 6). Hetastarch was used to control for any colloid effect. LR was used as positive control. Immediately after resuscitation, the lung was collected and evaluated for apoptosis by using two methods. TUNEL stain was used to determine general DNA damage, and Bax protein was used to specifically determine intrinsic pathway involvement. RESULTS: LR and hetastarch treatment resulted in significantly increased apoptosis in the lung as determined by both TUNEL and Bax expression (p < 0.05). Plasma infusion resulted in significantly less apoptosis than LR and hetastarch resuscitation. Multiple cell types (epithelium, endothelium, smooth muscle, monocytes) underwent apoptosis in the lung as demonstrated by the TUNEL stain, whereas Bax expression was limited to cells residing in the perivascular and peribronchial spaces. CONCLUSION: Apoptosis after volume resuscitation of hemorrhagic shock can be affected by the type of resuscitation fluid used. Manufactured fluids such as lactated Ringer's solution and 6% hetastarch resuscitation resulted in the highest degree of lung apoptosis. The plasma component of whole blood resulted in the least apoptosis. The process of apoptosis after hemorrhagic shock resuscitation involves the Bax protein.

Animals↗

Windows 99: a source of suburban pediatric trauma.

BACKGROUND: Falls from windows in urban areas cause a significant number of pediatric injuries. Window falls have not been well described in the nonurban setting. We describe the epidemiology of window falls from residential homes among pediatric patients at a suburban Level I trauma center. METHODS: A review of patients admitted from January 1991 through November 1999 to a center serving a rapidly growing suburban area was performed. RESULTS: A total of 2,322 children, ages 0-14 years, were admitted during the study period. Falls comprised 41% of these admissions, and 11% of falls were from windows, greater than twice the national average. More than 39% of children who fell from windows were admitted directly to the intensive care unit. Overall mortality rate was 4%. Ages 0 to 4 years comprised the largest percentage (83%), and all children who died were in this age group. Children < or = 4 years were more likely to have an Abbreviated Injury Score > or = 2 (head injury) than those ages 10 to 14 years (p = 0.032). More than 31% of all children injured in window falls seen at the study institution between 1991 and 1999 were admitted in the last 2 years. CONCLUSION: Pediatric falls from windows in this suburban area appear to be increasing, with an incidence greater than the national average. Children at greatest risk are less than 4 years old. Further research in injury prevention at the national level aimed at suburban areas may be warranted.

Accidental Falls↗

Genetic influence on laterality in schizophrenia? A twin study of neurological soft signs.

OBJECTIVE: This study explored the genetic basis of neurological soft signs in schizophrenia and addressed disturbed hemispheric lateralization. METHOD: The authors investigated neurological soft signs in 30 monozygotic twin pairs, 13 pairs discordant for schizophrenia or schizoaffective disorder and 17 healthy comparison twin pairs. RESULTS: The twins with schizophrenia showed higher total scores for neurological soft signs than did the comparison subjects. The total scores for neurological soft signs of the nonaffected discordant twins were significantly higher than those of the comparison twins. There was a significant difference between the nonaffected and affected discordant twins in total scores for neurological soft signs. In contrast to the comparison subjects, the nonaffected and affected twins of the discordant pairs showed a trend toward higher scores for neurological soft signs on the left body half. CONCLUSIONS: These results suggest that the occurrence of neurological soft signs and, more specifically, their lateralization to the left body half are genetically transmitted.

Adult↗

Suggestive linkage of chromosome 10p to schizophrenia is not due to transmission ratio distortion.

The genome scan of the European-American schizophrenia families from the Human Genetics Initiative of the National Institute of Mental Health (NIMH) reported a suggestive linkage to chromosome 10p. Subsequently, Paterson and Petronis [1999] reported evidence for transmission ratio distortion on 10p to females. They suggested that transmission ratio distortion to females might have created spurious evidence for linkage to 10p. To address this issue, we reanalyzed our 10p data using only male-male affected sibling pairs. The two chromosome 10p markers that gave the most evidence for linkage in our prior report continued to show evidence for linkage: D10S1423 (NPL Z = 3.0, P = 0.001) and its neighbor D10S582 (NPL Z = 2.9, P = 0.002). These data suggest that our prior report of suggestive linkage of schizophrenia to markers on 10p cannot be attributed to the transmission ratio distortion to females reported by Paterson and Petronis. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:607-608, 1999.

Chromosomes, Human, Pair 10↗

Acid-base disorders in milk-fed calves with chronic indigestion.

Acid-base disorders were investigated in 50 calves with chronic indigestion and metabolic acidosis. In the calves that were unable to stand up, the acidosis was significantly more severe than in the calves that could stand up. The anion gap and four different components of the base excess were calculated by the method described by Fencl. The anion gap was high in more than half of the calves, and it was significantly associated with the base excess due to unidentified anions. However, in seven of the calves, the excess of unidentified anions would not have been detected without the calculations, which made it possible to measure the effect of sodium, chloride, plasma protein and unidentified anions on the acid-base balance. Twenty-four of the calves had a combination of hyperchloraemic and high anion gap metabolic acidosis. Changes in sodium and plasma protein concentrations had a minor impact on the calves' acid-base status.

Acid-Base Equilibrium↗

Domains of axin involved in protein-protein interactions, Wnt pathway inhibition, and intracellular localization.

Axin was identified as a regulator of embryonic axis induction in vertebrates that inhibits the Wnt signal transduction pathway. Epistasis experiments in frog embryos indicated that Axin functioned downstream of glycogen synthase kinase 3beta (GSK3beta) and upstream of beta-catenin, and subsequent studies showed that Axin is part of a complex including these two proteins and adenomatous polyposis coli (APC). Here, we examine the role of different Axin domains in the effects on axis formation and beta-catenin levels. We find that the regulators of G-protein signaling domain (major APC-binding site) and GSK3beta-binding site are required, whereas the COOH-terminal sequences, including a protein phosphatase 2A binding site and the DIX domain, are not essential. Some forms of Axin lacking the beta-catenin binding site can still interact indirectly with beta-catenin and regulate beta-catenin levels and axis formation. Thus in normal embryonic cells, interaction with APC and GSK3beta is critical for the ability of Axin to regulate signaling via beta-catenin. Myc-tagged Axin is localized in a characteristic pattern of intracellular spots as well as at the plasma membrane. NH2-terminal sequences were required for targeting to either of these sites, whereas COOH-terminal sequences increased localization at the spots. Coexpression of hemagglutinin-tagged Dishevelled (Dsh) revealed strong colocalization with Axin, suggesting that Dsh can interact with the Axin/APC/GSK3/beta-catenin complex, and may thus modulate its activity.

Adaptor Proteins, Signal Transducing↗