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Biomedical subjects

C Ulrich

Publications and source records attributed to C Ulrich.

At least 37 records · Page 2Linked to original sources

Epithelial malignancies in organ transplant patients: clinical presentation and new methods of treatment.

Transplantation of solid organs has been well established as a mode of therapy for the treatment of various end-stage organ diseases for many years. Up to now, it has benefited more than 1 million patients worldwide. The long-term success of organ transplantation depends particularly on the prevention of allograft rejection. Various regimens have been used to suppress hosts' cellular immune responsiveness to the grafted organs. Nowadays immunosuppressive therapies consist mainly in prednisolone, azathioprine, cyclosporine, anti-T-lymphocyte-globulin (ATG), anti-CD 3 antibody (OKT3) and substances of a new generation, such as tacrolimus or mycophenolic acid. However, not only the patient's reactivity to the graft is impaired, but also that to infectious organisms. Chronically altered immune responsiveness is especially associated with a dramatically increased risk of malignancy, most frequently non-Hodgkin's lymphoma and skin cancer. Within the first 5 years of immunosuppression 40% of transplant recipients experience premalignant skin tumors such as actinic keratoses and Bowen's disease, and also such skin cancers as squamous cell carcinomas and basal cell carcinomas. Quite often these have an aggressive biology and an uncommon morphology. Cancer is now responsible for a mortality rate of 5-8% in organ transplant patients. Various risk factors, such as exposure to sun and infections with oncogenic viruses (e.g. HPV) contribute to the already increased risk of dysplasia when lifelong immunosuppression is required. Prophylactic strategies therefore include the development of virus-like particles (VLPs) as anticancer vaccines, which might become a very interesting approach to preventing HPV-associated cancer. The prevention of precancerous conditions and mature skin cancers in grafted patients includes protective clothing and adequate protection of UV-exposed skin regions, including lips, from sunlight with appropriate sunscreen. Close dermatological surveillance through a specialized outpatient department should be ensured to detect potentially fatal skin malignancies at an early stage. Early treatment of precancerous lesions includes topical retinoids, such as tretionin, tazarotene or adapalene. A 5% fluorouracil cream is widely used but shows variable effects on manifest actinic keratoses. As cellular immunity seems to play the major part in the prevention and cure of malignant and premalignant cutaneous neoplasias as well as viral infections, a specific enhancement of the local immunity would be desirable. Imiquimod is one of a class of agents known as immune response modifiers. The drug has been shown to have both antiviral and antitumor activity. Application of immune response activators or modifiers such as imiquimod might be premising in the case of transplant recipients.

Humans↗

[Skin diseases in organ transplant patients].

In Germany 3273 visceral organs were transplanted in the year 2000. Together with patients grafted abroad, it is estimated that between 70,000 and 100,000 organ transplant patients are currently living in Germany. With the provision of lifelong immunosuppression the survival-time of these patients can exceed more than 20 years. In the first year following transplantation special emphasis is given to the prevention of viral, bacterial and fungal infections. Regular dermatological screening can provide early diagnosis of even systemic infections. An increased incidence of skin cancer parallels the extended survival rates of grafted patients. Within the first 5 years of immunosuppression 40% of these patients develop pre-malignant skin tumors such as actinic keratoses, dysplastic nevi, squamous cell carcinomas and basal cell carcinomas. Squamous cell carcinomas show an aggressive biology and an uncommon clinical morphology. The increased incidence of cancer is now responsible for a mortality rate of 5-8% in grafted patients. Against a background of lifelong immunosuppression, other risk factors include sun exposure and infections with oncogenic viruses. The rapidly growing numbers of allograft recipients as well as the rising long term survival rates of these patients demand the provision of high quality interdisciplinary and dermatological care in this field.

Humans↗

Antiferromagnetic ordering in superconducting YBa2Cu3O6.5.

Commensurate antiferromagnetic ordering has been observed in the superconducting high- Tc cuprate YBa2Cu3O6.5 ( Tc = 55 K) by polarized and unpolarized elastic neutron scattering. The magnetic peak intensity exhibits a marked enhancement at Tc. Zero-field muon-spin-resonance experiments demonstrate that the staggered magnetization is not truly static but fluctuates on a nanosecond time scale. These results point towards an unusual spin density wave state coexisting with superconductivity.

Journal Article↗

Internal fixation on the lower cervical spine--biomechanics and clinical practice of procedures and implants.

The decision to opt for a particular internal fixation procedure of a traumatized unstable lower cervical spine should be based on analysis and implementation of scientific and clinical data on the biomechanics of the intact, the unstable and the implant-fixed spine. The following recommendations for surgical stabilization of the lower cervical spine seem, therefore, to be justified. Firstly, the surgical procedure should be to bring about decompression, realignment, and stability. Secondly, the anterior approach should be the primary and preferred one. With regard to surgical and positioning technique, this access clearly involves fewer problems than the posterior approach; if required, unrestricted additional cord decompression can take place; implant fixation is technically simple, and the fusion is under direct compression, thus allowing optimal fusion healing. The awareness of instability and type of implant permits functional therapy, above all for the paraplegic patient. Thirdly, for traumatic conditions, posterior methods should be reserved for exceptional indications. The restriction to this approach is that the anterior column must be intact and a multi-segmental fixation must be used. Posterior fixation seems, therefore, to be more appropriate for degenerative, rheumatoid or tumorous instabilities than for traumatic instabilities. The cerclage wire technique depends on intact osseous posterior elements, while after laminectomy only implants fixed with screws can create safe stability. The disadvantages of the posterior access for the proprioception of the cervical muscles and the subjective symptoms of the patient are known and must be taken into account. Fourthly, combined techniques are indicated for highly unstable or particularly complex injuries. On the cervicothoracic junction, or in cases of Bechterew's disease, the decision is justifiably made in favor of this technique, which can be performed as a one-stage or two-stage operation. Finally, whenever possible, selection of the implant should take into account the foreseeable developments in diagnostic procedures, and therefore, in view of the modern imaging techniques likely to be used in any follow-up examinations required later, the implant chosen should be made of titanium.

Biomechanical Phenomena↗

The interleukin-10 promoter genotype determines clinical immune function in hemodialysis patients.

BACKGROUND: Immune dysfunction and the impaired hepatitis B vaccination response are complications of chronic renal failure that are tightly associated with inflammation induced by uremia and blood-membrane contacts. Proinflammatory cytokines, such as interleukin (IL)-6, are counter-regulated by IL-10 with a large interindividual variability. Part of the variability of cytokine production is genetically determined since polymorphisms in the cytokine gene promoters lead to high or low production. The aim of this study was to detect the genetic influence of the IL-10 promoter on immune function of chronic hemodialysis patients. METHODS: The IL-10 genotype (polymorphic bases at positions -1082 and -819) was determined in 272 chronic hemodialysis patients using highly specific PCR and related to the patients' response to a triple vaccination against hepatitis B. Secretion of IL-10 and IL-6 by peripheral blood leucocytes in vitro was determined by ELISA. RESULTS: The prevalence of the IL-10 genotypes in dialysis patients with well-preserved immune function (vaccination responders) was similar to the general population. In contrast, prevalence of the -1082G* allele (associated with high production of IL-10) was low in the nonresponders. The relative risk of vaccination nonresponse in patients homozygous for the -1082A* allele was 1.394 (95% CI, 1.091 to 1.781, P < 0.05) compared to those homozygous for -1082G*. There was no relationship between the IL-10 genotype and the type of renal disease. CONCLUSIONS: The IL-10 genotype determines IL-10 production in dialysis patients, which down-regulates uremia- and dialysis-induced chronic inflammation and helps to preserve immune defense functions.

Cytokines↗

Hepatotoxic substance(s) removed by high-flux membranes enhances the positive acute phase response.

BACKGROUND: Acute phase proteins (APPs) are enhanced in end-stage renal disease patients (ESRD) requiring dialysis treatment. They are involved in a variety of pathologic processes like muscle proteolysis, cachexia, regulation of appetite, and atherosclerosis. They are predictive for mortality. APPs are not only makers but also active substances. They are mainly produced in liver cells and are primarily, but not exclusively, regulated by proinflammatory cytokines. To what extent hepatic APPs are influenced by uremic toxins is still unclear. Therefore, we investigated the effects of different ultrafiltrates (UFs) on the synthesis of alpha1-acid glycoprotein (AGP) in HepG2 cells. METHODS: A cross-sectional as well as a crossover study with high-/low-flux membranes was conducted to investigate the impact of UFs on bioactivity of liver cell cultures. Metabolic activity (MTT test), cytotoxicity (lactate dehydrogenase release), and the positive APP AGP were measured in HepG2 cells. RESULTS: Cultured hepatocytes treated with UFs from high-flux membranes exhibited a higher cytotoxicity (18.6 +/- 0.3% high-flux vs. 13.9 +/- 0.2% low-flux, P < 0.001) and a lower metabolic activity (29.3% high-flux vs. 50.3% low-flux, P < 0.001) in comparison with low-flux UFs. In addition, enhanced APP secretion could be observed under costimulatory conditions (high-flux 5.0 +/- 0.7 vs. low-flux 3.1 +/- 0.6 ng/microg protein, P < 0.05). The effects of high- and low-flux UFs were strongly expressed at the beginning and were still significantly different after 120 minutes of hemodialysis (HD) treatment. The crossover experiments confirmed that UFs collected during high-flux HD had a higher capacity to stimulate AGP synthesis in liver cells. CONCLUSION: The effects of UFs from dialysis patients demonstrate that hepatotoxic substances can be removed by dialysis. Stimulating the acute phase response UF collected during high-flux HD had a higher impact on liver cells in comparison with low-flux UF. These substances are putative cofactors involved in cytokine regulation.

Acute-Phase Reaction↗

[Enterovesical fistula in diverticulitis].

Three men aged 52, 60, and 38 years, complained of dysuria and recurrent cystitis. One patient mentioned pneumaturia, a feature which later appeared to be present in all three. Ultrasound examination showed air in the bladder, and demonstrated the fistulous tract in two cases. Computed tomography identified the third fistula. In all 3 the enterovesical fistula was a complication of sigmoid diverticulitis. After sigmoid resection they recovered well. The key to the diagnosis of enterovesical fistula is to think of it. Pneumaturia and faecaluria are pathognomonic symptoms. Both ultrasound and computed tomography may be helpful in the diagnosis.

Adult↗

[Metaphyseal defect substitute: hydroxylapatite ceramic. Results of a 3 to 4 year follow up].

45 trauma patients with fracture-related metaphyseal bone defects filled with hydroxyapatite ceramic (Endobon) were followed for three to four years after surgery. Osseointegration of Endobon could be confirmed histologically in all biopsates, which could be obtained during scheduled reintervention for hardware removal. The objective of clinical and radiological follow-up was to evaluate the extent of ceramic remodeling as well as long-term implant outcome. Thirteen patients undergoing surgery in 1992 or 1993 were available for follow-up. None of these patients showed radiologic evidence of loss of bony reconstruction or HAC sintering, nor was there evidence of HAC resorption or fragmentation. Our results--with respect to the examined few patients--suggest that Endobon is useful for filling bony defects in carefully selected trauma patients if certain surgical technique prerequisites are met. Like cancellous autografts special alloplasts appear to go some way toward solving problems of defect filling encountered in clinical practice.

Adult↗

[Surgical treatment of injuries of the thoracolumbar transition. 2: Operation and roentgenologic findings].

The authors report on a prospective multicenter study with regard to the operative treatment of acute fractures and dislocations of the thoracolumbar spine (T10-L2). The study should analyze the operative methods currently used and determine the results in a large representative collective. This investigation was realized by the working group "spine" of the German Trauma Society. Between September 1994 and December 1996, 682 patients treated in 18 different traumatology centers in Germany and Austria were included. Part 2 describes the details of the operative methods and measured data in standard radiographs and CT scans of the spine. Of the patients, 448 (65.7%) were treated with posterior, 197 (28.9%) with combined posterior-anterior, and 37 (5.4%) with anterior surgery alone. In 72% of the posterior operations, the instrumentation was combined with transpedicular bone grafting. The combined procedures were performed as one-stage operations in 38.1%. A significantly longer average operative time (4:14 h) was noted in combined cases compared to the posterior (P < 0.001) or anterior (P < 0.05) procedures. The average blood loss was comparable in both posterior and anterior groups. During combined surgery the blood loss was significantly higher (P < 0.001; P < 0.05). The longest intraoperative fluoroscopy time (average 4:08 min) was noticed in posterior surgery with a significant difference compared to the anterior group. In almost every case a "Fixateur interne" (eight different types of internal fixators) was used for posterior stabilization. For anterior instrumentation, fixed angle implants (plate or rod systems) were mainly preferred (n = 22) compared to non-fixed angle plate systems (n = 12). A decompression of the spinal canal (indirect by reduction or direct by surgical means) was performed in 70.8% of the neurologically intact patients (Frankel/ASIA E) and in 82.6% of those with neurologic deficit (Frankel/ASIA grade A-D). An intraoperative myelography was added in 22% of all patients. The authors found a significant correlation between the amount of canal compromise in preoperative CT scans and the neurologic deficit in Frankel/ASIA grades. The wedge angle and sagittal index measured on lateral radiographs improved from -17.0 degrees and 0.63 (preoperative) to -6.3 degrees and 0.86 (postoperative). A significantly (P < 0.01) stronger deformity was noted preoperatively in the combined group compared to the posterior one. The segmental kyphosis angle improved by 11.3 degrees (8.8 degrees with inclusion of the two adjacent intervertebral disc spaces). A significantly better operative correction of the kyphotic deformity was found in the combined group. In 101 (14.8%) patients, intra- or postoperative complications were noticed, 41 (6.0%) required reoperation. There was no significant difference between the three treatment groups. Of the 2264 pedicle screws, 139 (6.1%) were found to be misplaced. This number included all screws, which were judged to be not placed in an optimal direction or location. In seven (1.0%) patients the false placement of screws was judged as a complication, four (0.6%) of them required revision. The multicenter study determines the actual incidence of thoracolumbar fractures and dislocations with associated injuries and describes the current standard of operative treatment. The efforts and prospects of different surgical methods could be demonstrated considering certain related risks. The follow-up of the population is still in progress and the late results remain for future publication.

Adolescent↗

External fixation in forearm shaft fractures.

External fixation for uncomplicated forearm fractures is rarely performed. The situation is different in a multiply injured patient or in a fracture with considerable soft tissue damage. In these cases the external fixator confers quick and efficient stabilisation which meets the requirements of adequate nursing and aids recovery of the general and local condition. Later change to an appropriate internal fixation procedure for definitive fracture treatment is recommended.

Adolescent↗

[Surgical treatment of injuries of the thoracolumbar transition. 1: Epidemiology].

The authors report on a prospective multicenter study with regard to the operative treatment of fractures and dislocations of the thoracolumbar spine. 18 traumatologic centers in Germany and Austria, forming the working group "spine" of the German Society of Trauma Surgery, are participating in this continuing study. Between September 1994 and December 1996 682 patients (64% male) with an average age of 39 1/2 (7-83) years were entered. The entry criteria included all patients with acute and operatively treated (within 3 weeks after trauma) fractures and dislocations of the thoracolumbar spine (Th 10-L 2). Part 1 of this publication outlines the protocol and epidemiologic data. The incidence of fractures and dislocations of the thoracolumbar spine and associated injuries were recorded according to a standardized protocol, as well as the different operative methods and complications, duration of hospital stay, rehabilitation and incapacity. The analysis of the clinical social and radiological course was a second focus. The most frequent mechanism of injury was a fall (50%) or traffic accident (22%). Most of the fractures occurred at the L 1 level (49%). All injuries were classified according to the ASIF (AO) classification. 65% sustained an A-type fracture (compression fracture). Associated injuries were observed in 35% and 6% were polytraumatized. Extremities and thorax were most frequently affected. Younger age and traffic accidents lead more often to C-type fracture (fracture dislocation) and polytrauma. An increased number of multisegmental or multilevel lesions were observed in polytraumatized patients. There were 16% with incomplete paraplegia (Frankel/ASIA B-D) and 5% with complete paraplegia (Frankel/ASIA A). The rate of patients with initial neurologic deficits significantly increased with the severity of spinal injury according to the Magerl classification. Until discharge a neurologic improvement (at least 1 Frankel/ASIA grade) was observed in 32% of the partially paralyzed (Frankel/ASIA B-D) and in 12% of the patients with complete paraplegia (Frankel/ASIA A). A neurologic deterioration occurred in 3 patients (0.4%). As a base for further follow-up and late results the individual starting point was determined by collecting relevant data of the patients' history: 277 (40.6%) patients suffered from simultaneous diseases, one half was spine related. At the time of injury 559 (82.0%) patients were employed; 429 (62.9%) doing manual work. 369 (54.1%) patients stated sportive activities before the injury and 561 (82.3%) designated their "back function" as normal. For the time before injury the patients scored an average of 93.4 points in the Hannover Spine Score (0-100 points concerning complaints and function of the back/spine).

Adolescent↗

[Biomechanical and clinical aspects of spondylodesis of the lower cervical spine. Methods and implants].

The break with the demand for maximum rigidity of implant fixation of a traumatized unstable lower cervical spine is based on analysis and implementation of scientific and clinical data on the biomechanics of the native, the unstable and the implant-fixed spinal column. In view of these facts, recommendations for stabilization of the lower cervical spine can presently be formulated as follows: The surgical procedure is to bring about decompression, restoration of form and stability. The anterior approach should be the primary and preferred one. With regard to surgical and positioning technique, this access clearly involves less problems than the posterior approach; if required, unrestricted additional cord decompression can take place; implant fixation is technically simple: and the awareness of instability and type of implant permits functional therapy, also and above all for the paraplegic patient. For traumatic conditions, posterior methods are reserved for exceptional indications, and being single procedures, they require the anterior column to be intact and a multisegmental procedure. They are therefore less recommendable for traumata but rather suitable for degenerative, rheumatoid or tumorous instabilities. The cerclage wire technique depends on intact, osseous posterior elements, while after laminectomy only screwed implants can secure safe stability. This disadvantage of the posterior access for the proprioception of the cervical muscles and the subjective well-being of the patient are known and to be taken into account. Combined techniques are indicated for highly unstable or particularly complex injuries. On the cervicothoracic junction or in cases of Bechterew's disease, the decision is justifiably made in favor of the technique, which ca be performed as one-stage or two-stage operation. Whenever possible, selection of the implant should take into account the foreseeable developments in diagnostic procedures; and therefore, with a view to follow-up examinations required later and to modern imaging techniques, the implant chosen should be made of titanium.

Biomechanical Phenomena↗

Left-hemispheric superiority for visuospatial orientation in homing pigeons.

To test for lateralisation of visuospatial orientation during homing, pigeons who had binocularly learned the homeward route from remote release sites were tested monocularly on either their left or their right eye for homing performance. In two experiments with three different release sites, birds using their right eye showed considerably better homing performance. If sun compass information was available, there was no difference in the direction of vanishing. Without this information, a difference between pigeons using their left or right eye emerged. Results show that visuospatial orientation in birds can be lateralised in favour of the left brain hemisphere and lend further support to the view that vision is important for pigeons homing on a familiar route. Cognitive mechanisms which might account for the observed pattern of lateralisation are discussed.

Animals↗

Hepatoactive substances eliminated by continuous venovenous hemofiltration in acute renal failure patients.

BACKGROUND: Acute renal failure (ARF) in critically ill patients is mostly part of a multi-organ failure. Therefore, the effects of renal replacement therapy on the liver are clinically important. We investigated the effects of ultrafiltrates of patients treated with continuous venovenous hemofiltration (CVVH) on liver cells in vitro. METHODS: Patients with ARF were consecutively treated with CVVH using Multiflow60 (group I) or FH66 filters (group II). They were comparable with respect to diagnosis, age, sex, laboratory parameters, and renal replacement treatment, but were different in daily diuresis, serum levels, and blood flow. Ultrafiltrates were collected within the first 10 minutes after change of hemofilter. Proliferation (bromodeoxyuridine), vitality (lactate dehydrogenase), and acute-phase protein secretion of HepG2 cells were measured. RESULTS: Ultrafiltrates changed liver cell function significantly compared with medium control. Proliferation (group I 29.8+/-5.2% vs. group II 48.4+/-6.6%, P < 0.05) and vitality (group I 78.7+/-2.0% vs. group II 87.6+/-1.7%, P < 0.01) of HepG2 cells were significantly different. On the one hand, the secretion of the negative acute-phase protein transferrin [group 13.1+/-0.2 (ng/microg protein) vs. group II 5.1+/-0.5 (ng/microg protein), P < 0.01] was significantly reduced by Multiflow60 ultrafiltrates. On the other hand, positive acute-phase protein alpha1-acid glycoprotein was significantly stimulated by Multiflow60 ultrafiltrates [group I 2.6+/-0.1 (ng/microg protein) vs. group II 1.7+/-0.1 (ng/microg protein), P < 0.001]. CONCLUSION: This study demonstrates hepatoactive mediators in the ultrafiltrates. They are hepatotoxic and influence acute-phase protein metabolism. Further studies have to elucidate the different effects in both groups and the analysis of the putative mediator(s). It remains a challenging task to consider therapeutic measures to optimize renal replacement therapy in critically ill patients.

Acute Kidney Injury↗

[Risk factors for the development of phlebitis in peripheral infusions].

OBJECTIVE: To study the incidence and risk factors of development of phlebitis caused by peripheral infusions. DESIGN: Prospective, descriptive. SETTING: Westindies Hospital, The Hague, the Netherlands. METHODS: For all 348 patients given infusions in a 6-week period the development of phlebitis, if any, and the contributing factors were studied. RESULTS: Phlebitis developed in 136 patients (39%), after an average of 2.9 days (range: 1-14). Risk factors were female sex, earlier phlebitis, insertion on the ventral surface of the forearm and administration of antibiotics via the infusion. These factors were not interdependent. No correlation was found between development of phlebitis and the size of the needle. CONCLUSION: Development of phlebitis depends on a number of factors. Timely removal of the infusion can prevent the development of phlebitis. Infusions should preferably be administered via the hand.

Adolescent↗