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Biomedical subjects

B Maier

Publications and source records attributed to B Maier.

At least 19 recordsLinked to original sources

Computer-assisted, fluoroscopy-based ventral spondylodesis of thoracolumbar fractures.

OBJECTIVE: To design and evaluate a novel computer-assisted, fluoroscopy-based planning and navigation system for minimally invasive ventral spondylodesis of thoracolumbar fractures. MATERIALS AND METHODS: Instruments and an image intensifier are tracked with the SurgiGATE navigation system (Praxim-Medivision). Two fluoroscopic images, one acquired from anterior-posterior (AP) direction and the other from lateral-medial (LM) direction, are used for the complete procedure of planning and navigation. Both of them are calibrated with a custom-made software to recover their projection geometry and to co-register them to a common patient reference coordinate system, which is established by attaching an opto-electronically trackable dynamic reference base (DRB) on the operated vertebra. A bi-planar landmark reconstruction method is used to acquire deep-seated anatomical landmarks such that an intraoperative planning of graft bed can be interactively done. Finally, surgical actions such as the placement of the stabilization devices and the formation of the graft bed using a custom-made chisel are visualized to the surgeon by superimposing virtual instrument representations onto the acquired images. The distance between the instrument tip and each wall of the planned graft bed are calculated on the fly and presented to the surgeon so that the surgeon could formalize the graft bed exactly according to his/her plan. RESULTS: Laboratory studies on phantom and on 27 plastic vertebras demonstrate the high precision of the proposed navigation system. Compared with CT-based measurement, a mean error of 1.0 mm with a standard deviation of 0.1 mm was found. CONCLUSIONS: The proposed computer assisted, fluoroscopy-based planning and navigation system promises to increase the accuracy and reliability of minimally invasive ventral spondylodesis of thoracolumbar fractures.

Algorithms↗

Traumatic injuries of the pelvis and thoracic and lumbar spine: does thin-slice multidetector-row CT increase diagnostic accuracy?

The objective is to evaluate different multidetector-row CT (MDCT) strategies for adequate classification of spinal and pelvic injuries. Seventy intubated patients after multiple trauma underwent conventional radiography (CR) and MDCT. Examinations included the pelvis (P), the lumbar spine (LS) and the thoracic spine (TS). Conventional radiographs, 3-mm (CT5) and 5-mm scans (CT3) and 3-mm and 5-mm scans combined with MPR (CT3R/CT5R) were compared to surgery, autopsy and clinical course. MDCT led to significantly better results than CR (P<0.01). Correlation coefficients were r=1.0 (CT3R), r=0.96 [TS] to r=1.0 [P/LS] (CT5R), r=0.8 [P] to r=1.0 [TS] (CT3), r=0.80 [P] to r=0.86 [TS] (CT5) and r=0.3 [TS] to r=0.69 [P] (CR). Fractures were identified by CT3R in 100% of cases, by CT5R in 95%, by CT3 in 90% [P]-100% [TS], by CT5 in 83.3% [LS]-90% [P] and by CR in 57.1% [TS]-87.2% [P]. Unstable fractures were identified in 100% by CT3R, CT5R and CT3, 85.7% [TS]-100% [P/LS] by CT5 and 57.1% [TS]-80% [P] by CR. Only overlapping thin-slice multiplanar reformation allows for an adequate classification of spinal and pelvic injuries and thus is highly emphasized in patients after severe blunt trauma.

Adult↗

Influence of gender on treatment and short-term mortality of patients with acute myocardial infarction in Berlin.

AIMS: Previous studies have shown higher hospital mortality rates in women, especially younger women, than in men. In light of the fact that myocardial infarction therapy is rapidly developing, and since gender-specific aspects have been discussed in detail during recent years, it was our goal to re-evaluate factors influencing hospital mortality rate, especially those involving gender-specific differences, in the city of Berlin, Germany. METHODS: We prospectively collected data from 5133 patients (3330 men and 1803 women) with acute myocardial infarction who were treated in 25 hospitals in Berlin during the years 1999 to 2002. RESULTS: During hospitalization the overall mortality rate was 18.6% among women and 8.4% among men. Women were older (mean age for men 62 years; women 73 years) and less likely to be married (men 74.6%; women 36.9%) than men. Women generally took longer to arrive at the hospital after infarction than did men (median time: men 2.0 h; women 2.6 h). Women furthermore demonstrated a higher proportion of diabetes (men 22.8%; women 36.5%) and hypertension (men 58.0%; women 69.3%). Reperfusion therapy (men 68.8%; women 49.7%) and administration of beta-blockers (men 76.0%; women 66.0%) took place less often for women than for men. A multivariate analysis revealed the following factors to be independent predictors of hospital mortality: age, gender, diabetes mellitus, hypercholesterolemia, pre-existing heart failure, pre-hospital cardiopulmonary resuscitation, cardiogenic shock and pulmonary congestion on admission, admission to a hospital with >600 beds, ST-elevation in the initial ECG, reperfusion therapy, as well as beta-blocker and ACE inhibitor treatment within 48 h of hospitalization. CONCLUSION: Even after adjustment in multivariate analysis, women with acute myocardial infarction still demonstrate a higher risk for in-hospital death than men.

Adult↗

[Prehospital emergency setting caused by hemorrhagic oropharyngeal bullae in a child with dystrophic epidermolysis bullosa Hallopeau-Siemens].

Two painful large hemorrhagic bullae developed within minutes of each other in a four-month-old infant with autosomal recessive inherited epidermolysis bullosa dystrophica Hallopeau-Siemens. There was no significant impairment of spontaneous respiration. The emergency physician sedated the infant with midazolam administered by the nasal route. A community pediatrician called for assistance opened a bulla, which impressively improved the symptoms and avoided the necessity of an admission to hospital. The presented case demonstrates the importance of exchange of information within the group of emergency physicians regarding rare diseases not only in rural areas. In our opinion its also helpful to involve colleagues in private practice into the emergency system.

Administration, Inhalation↗

Graft repair of the peroneal nerve restores histochemical profile after long-term reinnervation of the rat extensor digitorum longus muscle in contrast to end-to-end repair.

Declining motor function is a prominent feature of ageing physiology. One reason for this is a reduction in plasticity that normally compensates for ongoing reorganization of motor units under physiological conditions. Previous work from our laboratory has shown that microsurgical repair of the transected peroneal nerve is followed by considerable changes in the histochemical profile of the reinnervated extensor digitorum longus (EDL) muscle and that these changes are dependent on both the time and the type of nerve repair. At 6 months postoperatively, a trend toward reversibility could be discerned. In the present work, we analysed the long-term reorganization of histochemical motor unit distribution patterns 15 months after performing either end-to-end repair or grafting of the peroneal nerve in 3-month-old rats. In addition, the EDL muscles of an age-matched control group (age 18 months) were analysed for age-dependent changes. We observed a loss of histochemical organization of motor units leading to an additional fibre type (SDH-INT) in the control group. Fifteen months after end-to-end repair, the histochemical profile showed a decrease in fibre type IIA and an increase in fibre type SDH-INT (P < 0.05), indicating a profound histochemical disorganization of motor units. In contrast, nerve grafting largely restored the histochemical profile of reinnervated EDL muscles. Fibre type grouping was present after both types of nerve repair. These findings show that reorganization of the histochemical profile in reinnervated muscles is dependent on the time and type of nerve repair and is long lasting. In this study, grafting provided superior results compared with end-to-end repair. These long-term results after peripheral nerve repair are influenced by age-dependent changes. Accordingly, nerve repair reduces the normal functional plasticity of motor unit organization. This reduction is enhanced by increasing age.

Aging↗

Glucose oxidation by Gluconobacter oxydans: characterization in shaking-flasks, scale-up and optimization of the pH profile.

In this study, the advantage of a novel measuring device for the online determination of oxygen and carbon dioxide transfer rates in shaking-flasks is reported for glucose oxidation by Gluconobacter oxydans. In this fermentation process, this device was used for the characterization of the oxidation pattern of different strains. G. oxydans NCIMB 8084 forms 2,5-diketogluconate from d-glucose in a multi-stage process via three different membrane-bound dehydrogenases. This strain was chosen for a scale-up of the process from shaking-flasks to a 2-l stirred vessel. An enhancement of 2,5-diketogluconate production was realized by controlling the pH at different levels during the fermentation.

Biotechnology↗

[Relevance of CT-scans for pediatric head injuries].

AIM OF THE STUDY: Clinical evaluation of pediatric head injury is quite difficult and often cranial CT scans are performed. We investigated the relevance of CT scans in relation to the therapeutic outcome. METHODS: During a 5-year-period we retrospectively evaluated the results of x-ray and cranial CT scan in respect to primary clinical assessment and degree of head injury. RESULTS: From 408 children classified as mild head injury (GCS 15-13) 217 received CT scans with 2 presenting pathological intracranial findings, none of these children required neurosurgical treatment. Out of 29 children suffering from severe head injury (GCS <12) 12 suffered from intracranial bleeding, and 17 had intracranial bleeding and a skull fracture. CONCLUSION: Children encountering mild head injury combined with primary loss of consciousness or vomiting, require hospitalisation. Initial CCT did not lead to therapeutic consequences in this group. Children classified as severe head injury or multiple traumatized children need immediate cranial CT scan and hospitalisation.

Adolescent↗

Stretching single stranded DNA, a model polyelectrolyte.

The elastic properties of single stranded (ss)DNA, studied by pulling on an isolated molecule, are shown to agree with a recent model of ssDNA that takes into account base pairings and screened electrostatic repulsion of the phosphodiester backbone. By an appropriate physicochemical treatment, the pairing interactions were suppressed and ssDNA used as an experimental model for a generic polyelectrolyte. The elastic behavior of such an altered ssDNA deviates strongly from the behavior of an ideal polymer. This deviation is shown to result from the elasticity of the chain and its electrostatic self-avoiding interactions.

DNA, Single-Stranded↗

[When does a pediatric fracture become a fracture of the adult? Age and significance of epiphyseal closures].

Surgical treatment of fractures of adolescents is often difficult as the epiphyses are still open or not yet completely closed. The osteosynthesis chosen has to consider the remaining prospective growth of the affected bone and biomechanical needs. Due to high physical maturity with small remaining growth capacity in adolescents, a number of different techniques known from osteosynthesis in adults with minor modifications can be used to treat these fractures.

Adolescent↗

Alterations of norepinephrine levels in plasma and CSF of patients after traumatic brain injury in relation to disruption of the blood-brain barrier.

BACKGROUND: In injured brain tissue with a disrupted blood-brain barrier (BBB) catecholamines such as norepinephrine (NE) are known to enhance glucose consumption and cerebral blood flow but may lead to an energy depletion increasing the risk of ischemia. Therefore it is of great interest whether the exogenous administration of NE used mainly to maintain an adequate cerebral perfusion pressure influences CSF NE levels or not, and whether elevated plasma or CSF levels of NE can influence the actual clinical condition. We addressed this issue by measuring the levels of NE in CSF and plasma and correlating them with the actual clinical condition of the patients. METHODS: In 29 patients with severe TBI (< 8 points on the Glasgow Coma Scale, GCS) NE levels were analysed by high performance liquid chromatography (HPLC) in paired blood and CSF specimens which were collected from days 1 to 14 after severe TBI (total number of pairs = 121). The integrity of the BBB was evaluated by determining the CSF/serum albumin ratio. The clinical condition of the patients was assessed by GCS. RESULTS: Elevated plasma and CSF NE levels were observed in 50% of all samples, most consistently in patients treated with NE. NE elevation in CSF was independent of whether or not the BBB remained intact. There was no correlation between GCS and the levls of NE in CSF or plasma either in samples from the treated or the untreated group. INTERPRETATION: Exogenous administration of NE seems to increase NE levels in plasma and CSF. However, in this group of patients with severe TBI there was no clinical evidence that exogenous administration of NE was detrimental to the traumatized patients.

Adolescent↗

Cerebral blood flow velocity and inflammatory response after severe traumatic brain injury.

OBJECTIVES: The cerebral blood flow velocity (CBVF) was measured by transcranial Doppler sonography in patients with severe traumatic brain injury (TBI) in order to determine, whether it depends on the posttraumatic inflammatory response. MATERIAL AND METHODS: CBVF in both middle cerebral arteries (MCA) was recorded in 25 comatous TBI patients (male 20; female five; mean age +/- standard deviation (S.D.), 41 +/- 20 years) and correlated to the levels of interleukine-(IL) 6, IL-8 and IL-10 in corresponding CSF/plasma samples, to PaCO2 and to intracranial (ICP), mean arterial (MAP) and cranial perfusion pressure (CPP). RESULTS: CSF IL-6 and IL-8 were clearly higher than the corresponding plasma levels (mean CSF/plasma quotient for IL-6: 159 +/- 582; for IL-8: 143 +/- 311). CBVF did not show large side-to-side differences at each examination indicating that CBFV in both MCAs was determined mostly by systemic conditions and not by severe regional abnormalities. Since all other evaluated variables including interleukines represent also systemic conditions we used the mean value (MCBFV) of both CBFVs for analysis. By stepwise regression analysis between MCBVF (mean +/- S.D., 80 +/- 26 cm/s) and the variables PaCO2 (33 +/- 4 mmHg), MAP (86 +/- 12 mmHg), ICP (20 +/- 11 mmHg), CPP (70 +/- 14 mmHg) and CSF or plasma IL-6, IL-8 and IL-10, it turned out that MCBFV correlated significantly with PaCO2 (r = 0.478; P < 0.01) and CSF IL-8 (r = -0.361; P < 0.05). CONCLUSIONS: When CPP is adequate for brain perfusion, CBFV in large brain supplying arteries depends predominantly on PaCO2 and shows only a slight association to intrathecal IL-8 levels. For clinical interpretation of CBFV data, the inflammatory response seems to be of minor relevance.

Adult↗

Differential release of interleukines 6, 8, and 10 in cerebrospinal fluid and plasma after traumatic brain injury.

Traumatic brain injury (TBI) is characterized by a high mortality which is largely determined by the initial cerebral trauma, secondary brain injury or indirectly during a Multiple Organ Dysfunction Syndrome (MODS). Therefore, we analyzed IL-6, IL-8, and IL-10 in cerebrospinal fluid (CSF) and in plasma with respect to blood-brain barrier (BBB) integrity in 29 patients suffering from isolated TBI. IL-6 and IL-8 were significantly increased compared to baseline levels early after trauma in CSF and plasma. In all patients CSF IL-6 and IL-8 were found to be higher than corresponding plasma levels. IL-10 in plasma was significantly increased above control plasma values, however, without a significant difference to the corresponding CSF values. BBB dysfunction was temporary present in 23 patients. Significant correlations between BBB dysfunction and cytokines were not found. Thus, alterations of the BBB seems not to influence the distribution pattern of interleukines in CSF and plasma after trauma.

Adolescent↗

Design and use of an inducibly activated human immunodeficiency virus type 1 Nef to study immune modulation.

The Nef protein of the human immunodeficiency virus type 1 (HIV-1) has been shown to enhance the infectivity of virus particles, downmodulate cell surface proteins, and associate with many intracellular proteins that are thought to facilitate HIV infection. One of the challenges in defining the molecular events regulated by Nef has been obtaining good expression of Nef protein in T cells. This has been attributed to effects of Nef on cell proliferation and apoptosis. We have designed a Nef protein that is readily expressed in T-cell lines and whose function is inducibly activated. It is composed of a fusion between full-length Nef and the estrogen receptor hormone-binding domain (Nef-ER). The Nef-ER is kept in an inactive state due to steric hindrance, and addition of the membrane-permeable drug 4-hydroxytamoxifen (4-HT), which binds to the ER domain, leads to inducible activation of Nef-ER within cells. We demonstrate that Nef-ER inducibly associates with the 62-kDa Ser/Thr kinase and is localized to specific membrane microdomains (lipid rafts) only after activation. Using this inducible Nef, we also compared the specific requirements for CD4 and HLA-A2 downmodulation in a SupT1 T-cell line. Half-maximal downmodulation of cell surface CD4 required very little active Nef-ER and occurred as early as 4 h after addition of 4-HT. In contrast, 50% downmodulation of HLA-A2 by Nef required 16 to 24 h and about 50- to 100-fold-greater concentrations of 4-HT. These data suggest that HLA-A2 downmodulation may require certain threshold levels of active Nef. The differential timing of CD4 and HLA-A2 downmodulation may have implications for HIV pathogenesis and immune evasion.

Animals↗

Replication by a single DNA polymerase of a stretched single-stranded DNA.

A new approach to the study of DNA/protein interactions has been opened through the recent advances in the manipulation of single DNA molecules. These allow the behavior of individual molecular motors to be studied under load and compared with bulk measurements. One example of such a motor is the DNA polymerase, which replicates DNA. We measured the replication rate by a single enzyme of a stretched single strand of DNA. The marked difference between the elasticity of single- and double-stranded DNA allows for the monitoring of replication in real time. We have found that the rate of replication depends strongly on the stretching force applied to the template. In particular, by varying the load we determined that the biochemical steps limiting replication are coupled to movement. The replication rate increases at low forces, decreases at forces greater than 4 pN, and ceases when the single-stranded DNA substrate is under a load greater than approximately 20 pN. The decay of the replication rate follows an Arrhenius law and indicates that multiple bases on the template strand are involved in the rate-limiting step of each cycle. This observation is consistent with the induced-fit mechanism for error detection during replication.

Base Sequence↗

Multiple cross-reactive self-ligands for Borrelia burgdorferi-specific HLA-DR4-restricted T cells.

T cell recognition of self antigens is a key event in the pathogenesis of autoimmune diseases. To date, the initial events that trigger autoreactive T cells are unknown. The "molecular mimicry" hypothesis predicts that during an infection T cells that recognize both a microbial antigen and a related self peptide become activated and cause autoimmune disease. We have systematically examined the recognition of self antigens by HLA-DR4-restricted T cells specific for peptides of the outer surface protein A (OspA) of Borrelia burgdorferi, the etiological agent of Lyme disease. We used the peptide spot synthesis technique for complete peptide substitution analyses of two immunodominant OspA epitopes. Each amino acid residue of the epitopes was substituted with all 20 naturally occurring amino acids and the altered peptides were tested for recognition by a panel of OspA-specific T cells. The binding motifs (supertopes) revealed by these analyses were used to screen public databases for matching human or murine peptides. Several hundred peptides were identified by this search and synthesized. Of these, 28 were recognized by OspA-specific T cells. Thus, T cell cross-reactivity is a common phenomenon and the existence of cross-reactive epitopes alone does not imply molecular mimicry-mediated pathology and autoimmunity.

Animals↗

[Severe craniocerebral trauma in multiple trauma. An assessment of the interaction of local and systemic mediator responses].

Isolated severe head trauma (SHT) or SHT in combination with multiple injuries are important factors for the prognosis of morbidity and mortality in patients suffering from the consequences of accidents. The prognosis mainly depends on the presence of primary mechanic brain injury and the development of secondary brain damage. Causes for the development of secondary brain damage are the intracranial space demand after traumatic injury and edema formation which may result in iscemia, as well as inflammatory processes. Both isolated SHT and polytrauma with or without brain damage may result in a systemic inflammatory response syndrome (SIRS) due to the synthesis of cytokines and other inflammatory mediators which may cause a single or multiple organ failure (MOF). Often the organism is able to survive isolated traumatic injuries and functional disturbances, but in combination or cumulation they may be lethal. The hypermetabolism after SHT is often regarded as an interaction between the central nervous system and the whole organism by the activation of the neuroendocrine axis. In contrast to the consequences of SHT for the whole organism, multiple injuries after polytrauma may affect brain functions, such as the shock dependent disturbance of the brain perfusion accompanied by brain hypoxia which may lead to an aggravated prognosis. Moreover, coagulation, metabolism and fracture healing are influenced by the onset of SIRS as well. Our knowledge about the bidirectional inflammatory interaction between brain and whole organism is still limited. In this context, the effects of secondary surgical interventions which may additionally, stress a traumatized body have to be considered and are the subject for actual clinical discussions and experimental studies. This article tries to summarize some important aspects on this topic.

Brain Injuries↗

Human T-cell leukemia virus type 1 Tax shuttles between functionally discrete subcellular targets.

Human T-cell leukemia virus type 1 (HTLV-1) Tax is a nuclear protein with striking pleiotropic functionality. We recently demonstrated that Tax localizes to a multicomponent nuclear speckled structure (Tax speckled structure [TSS]). Here, we examine these structures further and identify a partial overlap of TSS with transcription hot spots. We used a strategy of directed expression via fusion proteins to determine if these transcription sites are the subtargets within TSS required for Tax function. When fused to human immunodeficiency virus type 1 (HIV-1) Tat, the resulting Tat-Tax fusion protein displayed neither a Tat-like nor a Tax-like pattern but rather was targeted specifically to the transcription subsites. The Tat-Tax fusion was able to activate both the HIV-1 long terminal repeat (LTR) and the HTVL-1 LTR at the same level as the individual component; thus, targeting proteins to transcription hot spots was compatible with both Tax and Tat transcription function. In contrast, the fusion with HIV-1 Rev, Rev-Tax, resulted in a pattern of expression that was largely Rev-like (nucleolar and cytoplasmic). The reduced localization of Rev-Tax to transcription sites was reflected in a 10-fold drop in activation of the HTLV-1 LTR. However, there was no loss in the ability of Tax to activate via NF-kappaB. Thus, NF-kappaB-dependent Tax function does not require targeting of Tax to these transcription sites and suggests that activation via NF-kappaB is a cytoplasmic function. Selective mutation of the nuclear localization signal site in the Rev portion resulted in retargeting of Rev-Tax to TSS and subsequent restoration of transcription function, demonstrating that inappropriate localization preceded loss of function. Mutation of the nuclear export signal site in the Rev portion had no effect on transcription, although the relative amount of Rev-Tax in the cytoplasm was reduced. Finally, in explaining how Tax can occupy multiple subcellular sites, we show that Tax shuttles from the nucleus to the cytoplasm in a heterokaryon fusion assay. Thus, pleiotropic functionality by Tax is regulatable via shuttling between discrete subcellular compartments.

Blotting, Western↗

Structure and function of the ion channel ICln.

Normal function of organs and cells is tightly linked to the cytoarchitecture. Control of the cell volume is therefore vital for the organism. A widely established strategy of cells to counteract swelling is the activation of chloride and potassium channels, which leads to a net efflux of salt followed by water - a process termed regulatory volume decrease. Since there is evidence for swelling-dependent chloride channels (IClswell) being activated also during pathological processes, the identification of the molecular entity underlying IClswell is of utmost importance. Several proteins are discussed as the channel forming IClswell, i.e. phospholemman, p-glycoprotein, CLC-3 and ICln. In this review we would like to focus on the properties of ICln, a protein cloned from a Madin Darby canine kidney (MDCK) cell library whose expression in Xenopus laevis oocytes resulted in a nucleotide sensitive outwardly rectifying chloride current closely resembling the biophysical properties of IClswell.

Amino Acid Sequence↗