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Biomedical subjects

G Klima

Publications and source records attributed to G Klima.

At least 19 recordsLinked to original sources
PubMed2006

Efficacy of fibrinogen and prothrombin complex concentrate used to reverse dilutional coagulopathy--a porcine model.

BACKGROUND: This study was conducted to assess whether the combined administration of fibrinogen and prothrombin complex concentrate (PCC) enables the reversal of dilutional coagulopathy resulting from intended blood loss and fluid replacement, and whether this treatment reduces further blood loss and mortality. METHODS: In 20 anaesthetized pigs, approximately 65% of the estimated blood volume was withdrawn and replaced with the same amount of hydroxyethyl starch (6% HES 130/0.4) to mimic blood loss and to develop a dilutional coagulopathy. Pigs (randomized) received either fibrinogen (200 mg kg(-1)) and PCC (35 IU kg(-1)) (n=10), or placebo (n=10). Thereafter, a standard liver laceration was performed to induce uncontrolled haemorrhage. The subsequent blood loss and survival time were determined as primary outcome variables. Throughout the experiment serial blood samples were obtained to assess the competence of the haemostatic system using standard coagulation tests, modified Thrombelastograph measurements (ROTEM) and electron microscopy clot imaging. RESULTS: As compared with baseline, after haemodilution both groups showed statistically significant impairment of haemostasis as measured with standard coagulation tests and thrombelastography. These parameters significantly improved after administration of the study drugs while aPPT measurements remained unchanged. Blood loss after liver injury was significantly less in the treatment group as compared with placebo: 240 ml (50-830) vs 1800 ml (1500-2500) (P<0.0001). All treated animals survived, whereas 80% of the placebo group died (P<0.0001). CONCLUSION: During haemodilution, substitution of fibrinogen and PCC causes an enhancement of coagulation and final clot strength. This reversal of dilutional coagulopathy may reduce blood loss and mortality when large amounts of colloids are needed to maintain normovolaemia during huge blood losses.

Animals↗
PubMed2005

Effect of fibrinogen on reversal of dilutional coagulopathy: a porcine model.

BACKGROUND: This study was conducted to determine whether replacement of fibrinogen is useful in reversing dilutional coagulopathy following severe haemorrhage and administration of colloids. METHODS: In 14 anaesthetized pigs, approximately 65% of the estimated blood volume was withdrawn and replaced with the same amount of gelatin solution to achieve dilutional coagulopathy. Animals were randomized to receive either 250 mg kg(-1) fibrinogen (n=7) or normal saline (n=7). A standardized liver injury was then inflicted to induce uncontrolled haemorrhage. Modified thrombelastography and standard coagulation tests were performed at baseline, after blood withdrawal, after dilution, after injection of the study drugs, and on conclusion of the protocol. Further, electron microscopy imaging of the blood clots was performed and blood loss after liver injury was determined. RESULTS: Severely impaired haemostasis was observed after haemodilution with gelatin substitution. With administration of fibrinogen, clot firmness and dynamics of clot formation reached baseline values. Median blood loss following liver injury was significantly less (P=0.018) in the fibrinogen-treated animals (1100 ml; 800-1400 ml) than in the placebo group (2010 ml; 1800-2200 ml). CONCLUSIONS: Replacing 65% of the estimated blood volume with gelatin in swine resulted in dilutional coagulopathy; subsequent fibrinogen administration improved clot formation and reduced blood loss significantly.

Animals↗
PubMed2004

[Stem cell therapy for urinary incontinence].

Experimental and clinical studies investigated whether urinary incontinence can be effectively treated with transurethral ultrasound-guided injections of autologous myoblasts and fibroblasts.This new therapy was performed in eight female pigs. It could be shown that the injected cells survived well and that new muscle tissue was formed. Next, 42 patients (29 women, 13 men) suffering from urinary stress incontinence were treated. The fibroblasts were mixed with a small amount of collagen as carrier material and injected into the urethral submucosa to treat atrophies of the mucosa. The myoblasts were directly injected into the rhabdosphincter to reconstruct the muscle and to heal morphological and functional defects. In 35 patients urinary incontinence could be completely cured. In seven patients who had undergone multiple surgical procedures and radiotherapy urinary incontinence improved. No side effects or complications were encountered postoperatively. The experimental as well as the clinical data clearly demonstrate that urinary incontinence can be treated effectively with autologous stem cells. The present data support the conclusion that this new therapeutic concept may represent a very promising treatment modality in the future.

Adult↗
PubMed2004

A comparative study of three different biomaterials in the engineering of skeletal muscle using a rat animal model.

Defects caused by traumatic or postsurgical loss of muscle mass may result in severe impairments of the functionality of skeletal muscle. Tissue engineering represents a possible approach to replace the lost or defective muscle. The aim of this study was to compare the suitability of three different biomaterials as scaffolds for rat myoblasts, using a new animal model. PKH26-fluorescent-stained cultured rat myoblasts were either seeded onto polyglycolic acid meshes or, alternatively, suspended in alginate or in hyaluronic acid-hydrogels. In each of the eight Fisher CDF-344 rats, four capsule pouches were induced by subcutaneous implantation of four silicone sheets. After two weeks the silicone sheets were removed and myoblast-biomaterial-constructs were implanted in the preformed capsules. Specimens were harvested after four weeks and examined histologically by H&E-staining and fluorescence microscopy. All capsules were well-vascularized. Implanted myoblasts fused by forming multinucleated myotubes. This study demonstrates that myoblasts seeded onto different biomaterials can be successfully transplanted into preformed highly vascularized capsule pouches. Our animal model has paved the way for studies of myoblast-biomaterial transplantations into an ectopic non-muscular environment.

Absorbable Implants↗
PubMed2002

The seventh prototype of the mini-spindle-pump: does it fulfill the expectations of a short-term pump?

According to recent trends to develop implantable nonpulsatile blood pumps for different function modes and times, our intention was and still is to build a Mini-Spindle-Pump for a pumping duration of about 14 days. Initial conception for this plan was the premise that the device in a mock circuit should move 4 L of water/min at a speed of 12,000 to 15,000 rpm against a pressure difference of 90 mm Hg between pump inlet and outlet. Despite the development of 6 different prototypes, this project was not realized. Under the above-mentioned conditions, the main problem of this type of blood pump, the blood trauma, could not be reduced to an adequate level, i.e., the Mini-Spindle-Pump is not a high speed pump. Therefore, a revision of the conception was necessary. The device in a mock circuit should transport 5 L of water/min at a speed of about 9,000 rpm against a pressure difference of 90 mm Hg between its inlet and outlet. Considering the implantability of the blood pump, the following measurements for its components were arrived at. The U-shaped blockformed plexiglas housing was enlarged to 120 x 40 x 40 mm (length of blood chamber 86 mm, inner diameter 27 mm), and the rotor with 5 windings was redesigned at a length of 64 mm (outer diameter 25 mm, inner diameter 6.7 mm). In a mock circuit, this 7th prototype transported with a speed of 9,000 rpm about 10 L of water/min at an afterload of 80 mm Hg. In acute animal experiments with calves up to 15 h of pumping duration, the device showed the expected efficiency. Experiments with a longer pumping duration are necessary to confirm that this prototype will fulfill the criteria of a short-term pump according to Dr. Y. Nosé's advice.

Equipment Design↗
PubMed2002

The axillocoronary bypass. Blood flow and short-term graft histology in a porcine model.

BACKGROUND: Bypass grafts arising from the axillary artery may be indicated for complications during minimally invasive direct coronary artery bypass grafting, for redo operations and for management of a severely atherosclerotic ascending aorta. As basic data research on this technique is scanty, we investigated intraoperative function and postoperative morphology of axillocoronary bypass grafts in a porcine model. METHODS: Thirteen German domestic pigs received an axillocoronary vein graft (Group I, n=7) or an aortocoronary vein graft (Group II, n=6) to the left anterior descending artery. In Group I the proximal anastomosis was performed to the left axillary artery, and after partial rib resection the graft was brought transpleurally to the target vessel. In both groups the coronary anastomosis was carried out on the beating heart without cardiopulmonary bypass. Graft flow was measured using transit time ultrasonic flow probes. RESULTS: Intraoperatively all grafts showed a typical diastolic flow profile. Stable graft flow was lower in axillocoronary bypass grafts: 47 (30-60 mL/min) in Group I and 65 (35-126 mL/min) in Group II (p=0.005). Flow given as percentage of cardiac output, however, did not differ between the two grafts: 0.9 (0.6-1.2%) in Group I and 1.2 (0.8-2.4%) in Group II (p=NS). At day 4 after surgery there was no clear histologic predilection site for microtrauma and early degenerative changes in the axillocoronary graft. CONCLUSIONS: Axillocoronary bypass flow compares well with flow in the aortocoronary graft. Microtrauma after implantation and early degenerative changes in the axillocoronary vein bypass are not particularly impacted by the thoracic entry site.

Anastomosis, Surgical↗
PubMed2000

Improved technique for infrahepatic vena cava reconstruction in guinea pig-to-rat liver transplantation.

Guinea pig-to-rat orthotopic liver transplantation is associated with serious technical problems contributing to impaired graft perfusion and primary graft failure. In order to shorten the procurement procedure and thereby minimize liver damage before flushing, a simplified technique for infrahepatic caval reconstruction was developed. Dissection of the infrahepatic vena cava (IHVC) from adrenal glands and renal and lumbar veins represents the most difficult and time-consuming part of the donor operation, which is often not well tolerated by the animal; we avoided this step by using an isogeneic vena cava interposition graft (VCIG) following in situ perfusion. This graft is connected with the IHVC transsected just below the liver with a cuff technique. Donor operations lasted 15 to 20 minutes with the new technique (n = 7) compared to 52 to 76 minutes with conventional technique (n = 7). Reduced operating time was associated with markedly improved graft perfusion and significantly better graft survival. This modification of the donor procedure for the guinea pig-to-rat liver xenograft using a VCIG significantly reduces operating time and improves reperfusion and recipient survival.

Anastomosis, Surgical↗
PubMed2000

Reconstruction of the lower urinary tract using autologous muscle transfer and cell seeding: current status and future perspectives.

Functioning free-muscle transfer has established itself for the treatment of skeletal muscle deficiency over the last two decades. The capability of skeletal muscle to empty a spherical reservoir has been shown to be lessened if the muscle has contracted due to dissection. Currently there is no established curative treatment for bladder acontractility. Experimental data and preliminary clinical results have shown that innervated free latissimus dorsi muscle (LD) may serve as a substitute for a dysfunctional detrusor. In a clinical protocol, latissimus dorsi detrusor myoplasty (LDDM) was applied in 11 patients (age 9-68 years) with bladder acontractility due to spinal cord injury (seven patients), congenital malformations (two patients), detrusor myopathy (one patient), and idiopathic causes (one patient) who had required catheterization for bladder emptying for a minimum of 2 years. In all, 10 of 11 patients were capable of voiding volitionally, with eight of them no longer requiring catheterization, throughout the follow-up period of 12-46 months. Transplanted LD activity was confirmed by ultrasonography and flow-mode computerized tomography. It can thus be concluded that emptying of the bladder can be induced through the contractility of reinnervated free LD that has been wrapped around the bladder. An innervated free-LD flap does not undergo the severe muscle fibrosis, contracture, and atrophy that occur after transfer of completely or partially denervated pedicled muscle. Apart from the restoration of deficient detrusor function, microneurovascular transfer of a free-LD flap may be combined with tissue engineering to serve as a basis for bladder augmentation and substitution.

Adolescent↗
PubMed2000

Excellent coronary perfusion pressure during cardiopulmonary resuscitation is not good enough to ensure long-term survival with good neurologic outcome: a porcine case report.

PURPOSE: To report a case of cerebral ischemia confirmed by magnetic resonance imaging after successful cardiopulmonary resuscitation (CPR) complicated by acute respiratory injury. MATERIALS AND METHODS: After 4 min of cardiac arrest, followed by 3 min of basic life support CPR, a female pig weighing 38 kg received every 5 min vasopressin (0.4, 0.4 and 0.8 U/kg). After 22 min of cardiac arrest, including 18 min of CPR, one defibrillation attempt employing 100 J resulted in return of spontaneous circulation. Neurological evaluation was performed 24 and 96 h after successful CPR. Magnetic resonance imaging was carried out 4 days after CPR using a clinical 1.5 T scanner. The magnetic resonance imaging protocol consisted of fast spinecho T2-weighted, as well as spinecho T1-weighted imaging of the brain. RESULTS: CPR with vasopressin resulted in excellent coronary perfusion pressure ranging between 35 and 60 mm Hg throughout CPR. Eight minutes after initiation of chest compressions, bleeding out of the tracheal tube occurred. This was later confirmed as originating from bilateral bloody pulmonary infiltrations, resulting in acute respiratory injury in the post-resuscitation phase. Ninety-six hours after successful CPR, magnetic resonance imaging revealed bilateral diffuse cerebral vasogenic edema. CONCLUSION: Although excellent coronary perfusion pressure renders a return of spontaneous circulation more likely, complications such as acute respiratory injury in the post-resuscitation phase have to be managed carefully in order to ensure good neurological recovery from cardiac arrest.

Acute Disease↗
PubMed2000

Transplantation of IL-2-transduced murine bone marrow is associated with dose-dependent toxicity.

OBJECTIVE: The purpose of this study was to investigate the effects of interleukin-2 (IL-2) gene-transduced hematopoietic progenitor cells or cytotoxic function and systemic toxicity following syngeneic bone marrow transplantation. MATERIAL AND METHODS: Marrow of 5-fluorouracil pretreated donor mice were transfected with a retroviral vector containing the murine IL-2 gene and transplanted into lethally irradiated syngeneic hosts. RESULTS: Productive insertion of the IL-2 gene could be demonstrated at various intervals post-transplant without impairment of hematopoietic engraftment. Endogenously augmented IL-2 release resulted in a selective increase in CD4(+), CD8(+), and NK1.1(+) population in spleen and bone marrow, as well as significant cytolytic activity against syngeneic leukemia cells in vitro. Our results also illustrate the interdependence among the magnitude of systemic IL-2 levels, the number of IL-2-transduced cells in the transplant inoculum, and the appearance of systemic toxicity. Infusion of marrow transduced with high-titer, high-expressing IL-2 retrovirus resulted in significant morbidity and mortality in the recipients. Our studies demonstrate that mortality was secondary to severe lymphocytic infiltration of liver and lung, which was associated with increased expression of intercellular adhesion molecule-1 and vascular adhesion molecule-1. Reducing the number of IL-2-transduced cells in the bone marrow inoculum, however, resulted in significantly improved survival with no adverse events being evident during the post-transplant period. CONCLUSION: Delivery of IL-2 to the bone marrow can be achieved by transplantation of genetically modified hematopoietic cells, however, the overall feasibility is strongly influenced by the number of transduced cells in the bone marrow inocolum and/or the expression pattern of IL-2 in vivo.

Animals↗
PubMed2000

Survival with full neurologic recovery and no cerebral pathology after prolonged cardiopulmonary resuscitation with vasopressin in pigs.

OBJECTIVES: We sought to determine the effects of vasopressin and saline placebo in comparison with epinephrine on neurologic recovery and possible cerebral pathology in an established porcine model of prolonged cardiopulmonary resuscitation (CPR). BACKGROUND: It is unknown whether increased cerebral blood flow during CPR with vasopressin is beneficial with regard to neurologic recovery or detrimental owing to complications such as cerebral edema after return of spontaneous circulation. METHODS: After 4 min of cardiac arrest, followed by 3 min of basic life support CPR, 17 animals were randomly assigned to receive every 5 min either vasopressin (0.4, 0.4 and 0.8 U/kg; n = 6), epinephrine (45, 45 and 200 microg/kg; n = 6) or saline placebo (n = 5). The mean value +/- SEM of aortic diastolic pressure was significantly (p < 0.05) higher 90 s after each of three vasopressin versus epinephrine versus saline placebo injections (60 +/- 3 vs. 45 +/- 3 vs. 29 +/- 2 mm Hg; 49 +/- 5 vs. 27 +/- 3 vs. 23 +/- 1 mm Hg; and 50 +/- 6 vs. 21 +/- 3 vs. 16 +/- 3 mm Hg, respectively). After 22 min of cardiac arrest, including 18 min of CPR, defibrillation was attempted to achieve return of spontaneous circulation. RESULTS: All the pigs that received epinephrine and saline placebo died, whereas all pigs on vasopressin survived (p < 0.05). Neurologic evaluation 24 h after successful resuscitation revealed only an unsteady gait in all vasopressin-treated animals; after 96 h, magnetic resonance imaging revealed no cerebral pathology. CONCLUSIONS: During prolonged CPR, repeated vasopressin administration, but not epinephrine or saline placebo, ensured long-term survival with full neurologic recovery and no cerebral pathology in this porcine CPR model.

Animals↗
PubMed2000

[Sonography of the thyroid gland in practice and in the clinic].

Nowadays, the ultrasound examination is considered to be the most important procedure in the morphological examinations of the thyroid gland and its importance can be compared to the value of the basal thyroid stimulating hormone level (b-TSH) estimation in the examination of the thyroid function. Both methods in their preliminary stages can already exclude morphological and functional changes. In case of a disease, sonography makes the selection of further investigation procedures possible, in regard to their necessity and urgency. The organ size (in all 3 dimensions); the relationship to neighbouring structures; the echo pattern or the blood circulation are sonographic informations, which offer the specialist, the thyroid clinic or the surgeon (all with their wide differences of aims) an excellent means in the exclusion; the diagnosis; the investigation and the treatment strategy of thyroid gland diseases.

Humans↗
PubMed1999

Mucosal tissue oxygenation of the porcine jejunum during normothermic cardiopulmonary bypass.

Cardiopulmonary bypass (CPB) has been associated with intestinal tissue hypoxia, but direct measurements of mucosal oxygenation have not been performed. In anaesthetized pigs, jejunal mucosal oxygen tension and microvascular haemoglobin oxygen saturation were measured by a Clark-type electrode and tissue reflectance spectrophotometry. In pigs, normothermic CPB with systemic oxygen transport equivalent to baseline values was performed. In control animals, mucosal oxygen tension and mucosal haemoglobin oxygen saturation were mean 5.01 (SD 1.08) kPa and 38.0 (2.3)%, respectively. CPB was associated with a decrease in mucosal oxygen tension to 2.26 (1.21) kPa, decrease in mucosal microvascular haemoglobin oxygen saturation to 26.0 (3.9)% and appearance of oscillations in mucosal microvascular haemoglobin oxygen saturation. With CPB, arterial lactate concentrations increased from 1.77 (1.37) to 3.52 (1.58) mmol litre-1, but transvisceral lactate and splanchnic venous-arterial carbon dioxide tension gradients remained unchanged. Our results support the concept that CPB is associated with diminished oxygenation of intestinal mucosa that is probably caused by regional redistribution.

Animals↗
PubMed1998

Histological investigations on the Tyrolean Ice Man.

The 5,200-year-old Tyrolean Ice Man discovered in 1991 in the Otztal Alps is the world's most ancient known human glacier mummy. Histological investigation was aimed at 1) optimizing specimen preparation and 2) documenting the preservation state of (sub)cellular components. Minute pieces of frozen tissue were removed endoscopically from rib bone and cartilage, major blood vessels, oral cavity and alimentary tract, liver, spleen, diaphragm, respiratory system, femoral muscle and nerve, sympathetic trunk, brain, and skin. Double fixation with glutaraldehyde followed by osmium tetroxide and embedding in Epon/Araldite epoxy resins proved to be the method of choice for both light and transmission electron microscopy combined with classical histochemistry. In particular, mild evacuation of the desiccated tissue was determined to be essential to ensure homogeneous infiltration with fixatives and resins; as a result, sections of excellent quality could be obtained with any kind of sample. With regard to the preservation degree of (sub)cellular components, distinct tissue-specific patterns were observed. There were highly intact skeletal and connective tissues proper, however, most interestingly, there were remarkably intact nervous tissue components as well. By contrast, epithelial, muscle, and reticular connective tissues as well as blood had generally disintegrated due to autolysis, freeze/thaw damage, and adipocere formation. For a tentative interpretation of these patterns, we considered general aspects of cryopreservation, such as physicochemical properties of subcellular constituents and tissue physiology.

Adult↗
PubMed1998

2-Chlorodeoxyadenosine (cladribine) in combination with low-dose cyclosporin prevents rejection after allogeneic heart and liver transplantation in the rat.

The purine analogue 2-chlorodeoxyadenosine (2-CDA) has been shown to possess synergistic immunosuppressive properties when given together with cyclosporin (CSA) in a rat small bowel transplant model. The present study investigated the immunosuppressive potency of 2-CDA alone and in combination after liver or heart transplantation in a fully allogeneic rat model with 5 animals in each group. Immunosuppression was provided with CSA 10 mg/kg body weight (BW)/day orally or 2-CDA 0.1 mg/kg/BW day intravenously or both compounds together in the dosages mentioned. Animals were sacrificed on day 10 following transplantation, and graft histology was assessed. In addition, cardiac graft function was evaluated by palpation immediately prior to sacrificing the animal. CSA given alone was able to mitigate but not prevent rejection. 2-CDA alone did not exhibit any detectable immunosuppressive effect. When CSA was combined with 2-CDA, no rejection was seen in 80% of the liver allografts and in 60% of heart allografts, and only mild rejection was observed in the remaining animals. All hearts of the combined treatment group, however, beat strongly. From these findings it is concluded that 2-CDA alone has no, but together with CSA a strong immunosuppressive effect in preventing solid organ allograft rejection.

Animals↗