Biomedical subjects

C Kaufmann

Publications and source records attributed to C Kaufmann.

At least 19 recordsLinked to original sources

PubMed2007

The comparative effectiveness of anti-TNF therapy and methotrexate in patients with psoriatic arthritis: 6 month results from a longitudinal, observational, multicentre study.

OBJECTIVES: To compare the response to treatment with tumour necrosis factor (TNF) inhibitors and methotrexate (MTX) monotherapy in patients with psoriatic arthritis (PsA) within a real-life clinical setting. METHODS: We analysed data from an ongoing longitudinal, observational multicentre study in Norway. Our data comprised 526 cases of patients with PsA who received either anti-TNF treatment (n = 146) or MTX monotherapy (n = 380) and were followed for at least 6 months with measures of disease activity, health status and utility scores. A propensity score was computed to adjust for channelling bias. The changes in measures of disease activity and health-related quality of life from baseline to 3- and 6-month follow-up were compared between the groups with adjustments for the baseline value of the dependent variable and the propensity score (analyses of covariance (ANCOVA)). RESULTS: The groups were significantly different at baseline with respect to demographic and disease activity measures. The variables included in the propensity score were age, sex, number of previous disease modifying anti-rheumatic drugs (DMARDs), presence of erosive disease, treatment centre and investigator's global assessment. The adjusted changes at 6 months were significantly larger in the anti-TNF group for ESR, DAS-28, M-HAQ, patient's assessments of pain, fatigue and global disease activity on a visual analogue scale (VAS) and 4 out of 8 SF-36 dimensions. CONCLUSIONS: Clinical improvement was superior with TNF inhibitors compared to MTX monotherapy in patients with PsA, when assessed in this setting of daily clinical practice.

Adalimumab↗

PubMed2006

Adalimumab and methotrexate is more effective than adalimumab alone in patients with established rheumatoid arthritis: results from a 6-month longitudinal, observational, multicentre study.

OBJECTIVES: To compare the effectiveness of adalimumab monotherapy and adalimumab and methotrexate (MTX) combination therapy in patients with established rheumatoid arthritis. METHODS: Data from an ongoing longitudinal observational study in Norway were used to compare response to treatment with two different adalimumab regimens (monotherapy, n = 84; combination with MTX, n = 99). Patients were assessed with measures of disease activity, health status and utility scores. Within-group changes were analysed from baseline to follow-up at 3 and 6 months and the changes were compared between groups after adjustment for the propensity score. The groups were also compared for the proportions of patients achieving European League Against Rheumatism (EULAR) good response, Disease Activity Score (DAS)28 remission and treatment terminations. RESULTS: The improvement from baseline was significant for all measures in the adalimumab and MTX group, but only for DAS28, joint counts, two Short-form Health Survey with 36 questions (SF-36) dimensions and patient's and investigator's global assessment in the monotherapy group. All between-group differences were numerically in favour of combination therapy and significant for C reactive protein, joint counts, DAS28, Modified Health Assessment Questionnaire, investigator's global assessment, four SF-36 dimensions and Short Form 6D at 6 months. More patients in the combination therapy group reached EULAR good response (p<0.001) and remission (p = 0.07). At 6 months, 80.8% of the patients in the combination therapy group and 59.5% in the monotherapy group remained on treatment (p = 0.002). More withdrawals in the monotherapy group were due to adverse events. CONCLUSIONS: Our results were consistent across several categories of end points and suggest that adalimumab combined with MTX is effective in patients with rheumatoid arthritis treated in daily clinical practice and is superior to adalimumab monotherapy.

Adalimumab↗

PubMed2006

Laboratory evaluation of flight performance of the plum curculio (Coleoptera: Curculionidae).

Flight performance of laboratory-reared adults of the plum curculio, Conotrachelus nenuphar (Herbst) (Coleoptera: Curculionidae), was investigated under controlled conditions by using a flight mill system. Across all insects tested (n=198), median values of total distance traveled, total flight time, and maximum uninterrupted flight time were 122.7 m day(-1), 23.5 min day(-1), and 2.0 min, respectively. The latter result indicates that flight occurred primarily in short bursts. Although females had a significantly higher body mass than males, there were no significant differences in flight performance between the two sexes. Flight during the first 24-h test period (especially the first 6 h) was dominated by escape behavior, i.e., elevated levels of activity presumably associated with attempts by the insects to regain freedom of movement; during the second 24 h, flight activity was very limited throughout the late morning and afternoon, increased around sunset, and remained high during the night. All flight performance variables decreased linearly and significantly with insect age over the age range tested (2-16 d after emergence). Nutritional status also had a significant effect, whereby insects that had been provided with apples as a food source for 2 d after emergence showed considerably improved flight performance compared with those that had been given no food or only water during the same period. There was no significant effect of mating status on flight performance of male or female insects.

Animals↗

PubMed2006

Milk cortisol concentration in automatic milking systems compared with auto-tandem milking parlors.

Milk cortisol concentration was determined under routine management conditions on 4 farms with an auto-tandem milking parlor and 8 farms with 1 of 2 automatic milking systems (AMS). One of the AMS was a partially forced (AMSp) system, and the other was a free cow traffic (AMSf) system. Milk samples were collected for all the cows on a given farm (20 to 54 cows) for at least 1 d. Behavioral observations were made during the milking process for a subset of 16 to 20 cows per farm. Milk cortisol concentration was evaluated by milking system, time of day, behavior during milking, daily milk yield, and somatic cell count using linear mixed-effects models. Milk cortisol did not differ between systems (AMSp: 1.15 +/- 0.07; AMSf: 1.02 +/- 0.12; auto-tandem parlor: 1.01 +/- 0.16 nmol/L). Cortisol concentrations were lower in evening than in morning milkings (1.01 +/- 0.12 vs. 1.24 +/- 0.13 nmol/L). The daily periodicity of cortisol concentration was characterized by an early morning peak and a late afternoon elevation in AMSp. A bimodal pattern was not evident in AMSf. Finally, milk cortisol decreased by a factor of 0.915 in milking parlors, by 0.998 in AMSp, and increased by a factor of 1.161 in AMSf for each unit of ln(somatic cell count/1,000). We conclude that milking cows in milking parlors or AMS does not result in relevant stress differences as measured by milk cortisol concentrations. The biological relevance of the difference regarding the daily periodicity of milk cortisol concentrations observed between the AMSp and AMSf needs further investigation.

Animals↗

PubMed2005

Brain activation and hypothalamic functional connectivity during human non-rapid eye movement sleep: an EEG/fMRI study.

Regional differences in sleep EEG dynamics indicate that sleep-related brain activity involves local brain processes with sleep stage specific activity patterns of neuronal populations. Macroscopically, it is not fully understood which cerebral brain regions are involved in the successive discontinuation of wakefulness. We simultaneously used EEG and functional MRI on 9 subjects (6 female: mean = 24.1 years, 3 male: mean = 26.0 years) and analyzed local blood oxygenation level dependent signal changes linked to the transition from wakefulness to different non-rapid eye movement (NREM) sleep stages (according to Rechtschaffen and Kales) of the first sleep cycles after 36 h of total sleep deprivation. Several brain regions throughout the cortex, the limbic lobe, the thalamus, the caudate nucleus, as well as midbrain structures, such as the mammillary body/hypothalamus, showed reduced activity during NREM sleep across all sleep stages. Additionally, we found deactivation patterns specific to NREM sleep stages compared with wakefulness suggesting that a synchronized sleeping state can be established only if these regions interact in a well-balanced way. Sleep stage 2, which is usually linked to the loss of self-conscious awareness, is associated with signal decreases comprising thalamic and hypothalamic regions, the cingulate cortex, the right insula and adjacent regions of the temporal lobe, the inferior parietal lobule and the inferior/middle frontal gyri. The hypothalamic region known to be of particular importance in the regulation of the sleep-wake cycle shows specific temporally correlated network activity with the cortex while the system is in the sleeping state, but not during wakefulness. We describe a specific pattern of decreased brain activity during sleep and suggest that this pattern must be synchronized for establishing and maintaining sleep.

Adult↗

PubMed2004

Normalisation of ocular pulse amplitude after embolisation of dural cavernous sinus arteriovenous fistula.

BACKGROUND: The difference in the ocular pulse amplitude between an individual's eyes may reflect abnormalities of the cerebrovascular circulation and has been shown to be helpful in assessing patients with cavernous sinus arteriovenous fistulas. HISTORY AND SIGNS: A 71-year-old woman presented with episcleral injection, proptosis, bruit and retro-orbital pain on the left side. Ocular pulse amplitude as measured by dynamic contour tonometry was 4.38 +/- 1.23 mm Hg in the right and 9.57 +/- 2.71 mm Hg in the left eye. Angiography revealed the haemodynamics of a dural left cavernous sinus arteriovenous fistula. THERAPY AND OUTCOME: Successful occlusion of the fistula was performed by transvenous embolisation. After embolisation, ocular pulse amplitude was 2.84 +/- 0.60 mm Hg in the right and 1.88 +/- 0.29 mm Hg in the left eye. CONCLUSION: In this case of a dural arteriovenous fistula the ocular pulse amplitude as measured by dynamic contour tonometry parallels closely both clinical findings and neuroimaging.

Aged↗

PubMed2002

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↗

PubMed2001

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↗

PubMed2001

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↗

PubMed2001

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↗

PubMed2001

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↗

PubMed2001

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↗

PubMed2001

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↗

PubMed2001

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↗

PubMed2000

[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↗

PubMed2000

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↗

PubMed2000

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↗

PubMed2000

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↗