Search PubMed⌕ Search

Biomedical subjects

M Pfeiffer

Publications and source records attributed to M Pfeiffer.

At least 37 records · Page 2Linked to original sources

A new semirigid implant for instrumentation of scoliosis: preliminary report.

A new set of pedicle screws, lamina and pedicle hooks, longitudinal rods and a titanium cable was developed to overcome the increasingly obvious hazards of overly rigid spinal instrumentation. Results of the first 12 consecutive scoliosis patients with this new system are reported, with an average follow-up time of 18 months. No major complications occurred. The average correction of the deformity was well within the range of more rigid systems. The new Dorsal Dynamic Spondylodesis (DDS) system proved to be easy to use, fast, powerful, safe, versatile, and biomechanically sound. Reduction of stress-shielding effects and protection of adjacent segments can be expected, and the system warrants future application in selected prospective cases with long-term follow-up.

Equipment Design↗

The natural history of the growth of the hand: I. Hand area as a percentage of body surface area.

The use of a patient's own hand as a tool to estimate the area of burn injury is well documented. The area of the palmar surface of one hand has been estimated to be 1 percent of the body surface area. The area of the palmar surface of the hand was measured to test the accuracy of this estimate and then compared with the body surface area as calculated by formulas in common use. This study also sought to determine the natural history of the growth of the hand to permit development of a readily available, bedside means of estimating hand area and body surface area. Bilateral hand tracings were obtained from 800 volunteers ranging in age from 2 to 89 years. The area of each tracing was determined using an integrating planimeter. The height and weight of each individual were measured, and his/her body surface area was calculated. The palmar hand's percentage of body surface area was determined by calculating the quotient for hand area divided by body surface area. Additionally, the width of the hand was measured from the ulnar aspect at the palmar digital crease of the small finger to the point where the thumb rested against the base of the index finger. The length of the hand was measured from the middle of the interstylon to the tip of the middle finger. These two figures were multiplied together to obtain a product which approximated the area of the hand. Based on the most commonly used DuBois formula for calculating body surface area, the area of palmar surface of the hand corresponds to 0.78 +/- 0.08 percent of the body surface area in adults. The percentage varies somewhat with age and reaches a maximum of 0.87 +/- 0.06 percent in young children. Multiplying the length of the hand by its width overestimates the area of the hand as determined by planimetry by only 2 percent. A patient's own hand may be used as a complementary, readily available template for estimation of burn area or other areas of disease or injury. In adults, the area of tracing of the outline of the hand is 0.78 percent of the body surface area, whereas in children, this number tends to be slightly higher. In the emergency room or on the wards, a simple product of length multiplied by width of the hand will closely approximate the area as determined by planimetry. This method allows a more accurate determination of the area of the palmar surface of the hand than the 1 percent estimate, which may lead to an overestimation of the size of a burn wound in adults.

Adolescent↗

Immunological aspects of haploidentical stem cell transplantation in children.

Thirty-eight children with high-risk hematological malignancies underwent transplantation with megadoses of peripheral mobilized CD34+ cells from haploidentical parents (n = 24) or from matched unrelated donors (n = 14). The CD34+ cells were isolated to a purity of > 98% using magnetic-activated cell sorting. This high purity was associated with an almost complete depletion of T lymphocytes. No pharmacological prophylaxis for graft-versus-host disease (GvHD) was used, and significant primary GvHD was not seen. A final engraftment was seen in all patients. Sixteen patients are alive and disease-free with a median follow-up of 24 months. The immunological reconstitution was faster in the patients transplanted with CD34+ stem cells from the haploidentical donors compared to the matched unrelated donors, and the transplantation of large numbers of haploidentical CD34+ stem cells seems to be superior to that of the matched unrelated donors. The phenotypical and functional analysis of the immune reconstitution provided some insights into the biology of transplantation of highly purified CD34+ cells. In this article, we summarize our current results with the transplantation of highly purified stem cells and discuss possible implications for further antileukemic post-transplant therapeutic strategies.

Antibodies, Monoclonal↗

Prevalence of HSV-1 LAT in human trigeminal, geniculate, and vestibular ganglia and its implication for cranial nerve syndromes.

Herpes simplex virus type 1 (HSV-1) enters sensory neurons and can remain latent there until reactivation. During latency restricted HSV-1 gene expression takes place in the form of latency-associated transcripts (LAT). LAT has been demonstrated to be important not only for latency but also for reactivation, which may cause cranial nerve disorders. Tissue sections of the trigeminal ganglia (TG), geniculate ganglia (GG), and the vestibular ganglia (VG) from seven subjects were examined for the presence of LAT using the in situ hybridization technique. LAT was found on both sides in allTG (100%), on both sides of five subjects (70%) in the GG, and in none of the VG. Using a second more sensitive detection method (RT-PCR), we found LAT in the VG of seven of ten other persons (70%). This is the first study to demonstrate viral latency in the VG, a finding that supports the hypothesis that vestibular neuritis is caused by HSV-1 reactivation. The distribution of LAT in the cranial nerve ganglia indicates that primary infection occurs in the TG and GG and subsequently spreads along the faciovestibular anastomosis to the VG.

Adult↗

Changes in the surface structure of purple membrane upon illumination measured by atomic force microscopy.

Bacteriorhodopsin (BR) patches with a diameter of 1 to 3 µm were investigated in their native state by atomic force microscopy (AFM) in buffer solution. The patches were immobilized deposited and investigated on mica in 150 mM KCl and 10 mM Tris-buffer at pH 8. Under this buffer condition they adsorb preferred with their extracellular side to the solid support mica. The structure of the two-dimensional light adapted crystals was resolved with an imaging force of about 100 pN up to a resolution of 13 Å. The topography of the surface gets smoother if an imaging force of 1000 pN was applied indicating that protruding structures are compressed. Upon illumination with white light, during imaging with a force of 200 pN, the surface structure of the BR lattice changed. The force- and light-induced structural changes were reversible.

Journal Article↗

Homo- and heterodimerization of somatostatin receptor subtypes. Inactivation of sst(3) receptor function by heterodimerization with sst(2A).

Several recent studies suggest that G protein-coupled receptors can assemble as heterodimers or hetero-oligomers with enhanced functional activity. However, inactivation of a fully functional receptor by heterodimerization has not been documented. Here we show that the somatostatin receptor (sst) subtypes sst(2A) and sst(3) exist as homodimers at the plasma membrane when expressed in human embryonic kidney 293 cells. Moreover, in coimmunoprecipitation studies using differentially epitope-tagged receptors, we provide direct evidence for heterodimerization of sst(2A) and sst(3). The sst(2A)-sst(3) heterodimer exhibited high affinity binding to somatostatin-14 and the sst(2)-selective ligand L-779,976 but not to the sst(3)-selective ligand L-796,778. Like the sst(2A) homodimer, the sst(2A)-sst(3) heterodimer stimulated guanosine 5'-3-O-(thio)triphosphate (GTPgammaS) binding, inhibition of adenylyl cyclase, and activation of extracellular signal-regulated kinases after exposure to the sst(2)-selective ligand L-779,976. However, unlike the sst(3) homodimer, the sst(2A)-sst(3) heterodimer did not promote GTPgammaS binding, adenylyl cyclase inhibition, or extracellular signal-regulated kinase activation in the presence of the sst(3)-selective ligand L-796,778. Interestingly, during prolonged somatostatin-14 exposure, the sst(2A)-sst(3) heterodimer desensitized at a slower rate than the sst(2A) and sst(3) homodimers. Both sst(2A) and sst(3) homodimers underwent agonist-induced endocytosis in the presence of somatostatin-14. In contrast, the sst(2A)-sst(3) heterodimer separated at the plasma membrane, and only sst(2A) but not sst(3) underwent agonist-induced endocytosis after exposure to somatostatin-14. Together, heterodimerization of sst(2A) and sst(3) results in a new receptor with a pharmacological and functional profile resembling that of the sst(2A) receptor, however with a greater resistance to agonist-induced desensitization. Thus, inactivation of sst(3) receptor function by heterodimerization with sst(2A) or possibly other G protein-coupled receptors may explain some of the difficulties in detecting sst(3)-specific binding and signaling in mammalian tissues.

Adenylyl Cyclases↗

Conformations of the rhodopsin third cytoplasmic loop grafted onto bacteriorhodopsin.

BACKGROUND: The third cytoplasmic loop of rhodopsin (Rho EF) is important in signal transduction from the retinal in rhodopsin to its G protein, transducin. This loop also interacts with rhodopsin kinase, which phosphorylates light-activated rhodopsin, and arrestin, which displaces transducin from light-activated phosphorylated rhodopsin. RESULTS: We replaced eight residues of the EF loop of bacteriorhodopsin (BR) with 24 residues from the third cytoplasmic loop of bovine Rho EF. The surfaces of purple membrane containing the mutant BR (called IIIN) were imaged by atomic force microscopy (AFM) under physiological conditions to a resolution of 0.5-0.7 nm. The crystallinity and extracellular surface of IIIN were not perturbed, and the cytoplasmic surface of IIIN increased in height compared with BR, consistent with the larger loop. Ten residues of Rho EF were excised by V8 protease, revealing helices E and F in the AFM topographs. Rho EF was modeled onto the BR structure, and the envelope derived from the AFM data of IIIN was used to select probable models. CONCLUSIONS: A likely conformation of Rho EF involves some extension of helices E and F, with the tip of the loop lying over helix C and projecting towards the C terminus. This is consistent with mutagenesis data showing the TTQ transducin-binding motif close to loop CD, and cysteine cross-linking data indicating the C-terminal part of Rho EF to be close to the CD loop.

Amino Acid Sequence↗

High-field EPR studies of the structure and conformational changes of site-directed spin labeled bacteriorhodopsin.

Cw and pulsed high-field EPR (95 GHz, 3.4 T) are performed on site-directed spin labeled bacteriorhodopsin (BR) mutants. The enhanced Zeeman splitting leads to spectra with resolved g-tensor components of the nitroxide spin label. The g(xx) component shift determined for 10 spin labels located in the cytoplasmic loop region and in the protein interior along the BR proton channel reveals a maximum close to position 46 between the proton donor D96 and the retinal. A plot of g(xx) versus A(zz) of the nitrogen discloses grouping of 12 spin labeled sites in protic and aprotic sites. Spin labels at positions 46, 167 and 171 show the aprotic character of the cytoplasmic moiety of the proton channel whereas nitroxides at positions 53, 194 and 129 reveal the protic environment in the extracellular channel. The enhanced sensitivity of high-field EPR with respect to anisotropic reorientational motion of nitroxides allows the characterization of different motional modes for spin labels bound to positions 167 and 170. The motional restriction of the nitroxide at position 167 of the double mutant V167C/D96N is decreased in the M(N) photo-intermediate. An outward shift of the cytoplasmic moiety of helix F in the M(N) intermediate would account for the high-field EPR results and is in agreement with diffraction and recent X-band EPR data.

Bacteriorhodopsins↗

Unfolding pathways of individual bacteriorhodopsins.

Atomic force microscopy and single-molecule force spectroscopy were combined to image and manipulate purple membrane patches from Halobacterium salinarum. Individual bacteriorhodopsin molecules were first localized and then extracted from the membrane; the remaining vacancies were imaged again. Anchoring forces between 100 and 200 piconewtons for the different helices were found. Upon extraction, the helices were found to unfold. The force spectra revealed the individuality of the unfolding pathways. Helices G and F as well as helices E and D always unfolded pairwise, whereas helices B and C occasionally unfolded one after the other. Experiments with cleaved loops revealed the origin of the individuality: stabilization of helix B by neighboring helices.

Amino Acid Sequence↗

Hyperimmunoglobulin prophylaxis, monitoring and preemptive ganciclovir treatment eliminate the risk of CMV infection to improve patient and renal allograft survival.

This study was designed to investigate whether the introduction of ganciclovir to clinical use for anti-CMV treatment changes the risk of CMV infection in renal transplant patients. A total of 1545 cases who had received cadaveric renal transplants were divided into two groups: group 1 (n = 721) was made up of patients who received their transplants within 6 years before the introduction (1991) of ganciclovir and group 2 (n = 824), of individuals transplanted thereafter. Patient and graft survival of CMV D+/R- patients was uni- and multivariately compared with non-CMV D+/R- patients. In CMV D+/R- patients in group 1, survival was significantly lower, and their relative risk for graft loss was 1.32-fold (P = 0.0483) that of non-CMV D+/R- patients. In group 2 patient and graft survival was identical regardless of whether the patients were at risk for CMV infection or not. The risk of CMV infection can be eliminated by hyperimmunoglobulin prophylaxis, CMV monitoring and preemptive ganciclovir treatment in renal transplant patients.

Adult↗

Sodium bromide: effects on different patterns of epileptiform activity, extracellular pH changes and GABAergic inhibition.

Results regarding the anticonvulsant potency of bromide have been questioned, and the mechanisms of its action are unclear. Using combined rat hippocampus-entorhinal cortex slices we analyzed the effects of NaBr on four types of epileptiform discharges in two different models of epilepsy, the low-Ca2+ and the low-Mg2+ model. NaBr concentration-dependently reduced the frequency and finally blocked the low Ca2+-induced discharges. Low Mg2+-induced short recurrent discharges were also reduced in a concentration-dependent manner. In the entorhinal cortex the frequency of seizure-like events was reduced by 3 and 5 mM and the discharges were blocked by 7 mM NaBr. Also, the late recurrent discharges in the entorhinal cortex which do not respond to most clinically employed anticonvulsants were reduced by concentrations of 10 and 15 mM and completely blocked by 30 mM NaBr. Using pH-sensitive microelectrodes different effects of NaBr were seen than those of acetazolamide on extracellular pH under control conditions and after stimulation. Acetazolamide at 1 mM caused a reversible acidification of delta pH: 0.2+/-0.14 at rest whereas no change on extracellular pH was seen with 5 mM NaBr. Acetazolamide increased the transient alkalosis induced by repetitive stimulation of the stratum radiatum in area CA1 and reduced the subsequent acidosis. NaBr also increased the alkalosis but had no effect on the subsequent acidosis. A significant increase in paired-pulse inhibition was seen in a paired-pulse stimulation protocol used to monitor the efficacy of GABAergic inhibition at concentrations of 5 mM NaBr. This finding was confirmed in whole-cell patch clamp recordings from cultured hippocampal neurons showing an increase in inhibitory postsynaptic current amplitude. In summary, our results suggest a broad-spectrum anticonvulsant activity which is likely to be caused by its effects on membrane excitability, by an increase in GABAergic inhibition and is less likely caused by its effects on extracellular pH.

Acetazolamide↗

Unraveling photoexcited conformational changes of bacteriorhodopsin by time resolved electron paramagnetic resonance spectroscopy.

By means of time-resolved electron paramagnetic resonance (EPR) spectroscopy, the photoexcited structural changes of site-directed spin-labeled bacteriorhodopsin are studied. A complete set of cysteine mutants of the C-D loop, positions 100-107, and of the E-F loop, including the first alpha-helical turns of helices E and F, positions 154-171, was modified with a methanethiosulfonate spin label. The EPR spectral changes occurring during the photocycle are consistent with a small movement of helix C and an outward tilt of helix F. These helix movements are accompanied by a rearrangement of the E-F loop and of the C-terminal turn of helix E. The kinetic analysis of the transient EPR data and the absorbance changes in the visible spectrum reveals that the conformational change occurs during the lifetime of the M intermediate. Prominent rearrangements of nitroxide side chains in the vicinity of D96 may indicate the preparation of the reprotonation of the Schiff base. All structural changes reverse with the recovery of the bacteriorhodopsin initial state.

Amino Acid Sequence↗

[Study on quality assurance in the prevention and therapy of decubitus ulcer by measuring the overlay pressure with test subjects on different prophylaxis systems].

The aim of this study on quality assurance in prevention and treatment of bedsores was to analyse the current state of treatment of pressure sores at the University Hospital in Marburg. Measurements of pressure exerted on the skin were taken of six soft storage systems and five alternating pressure systems. In addition, the study aimed to find out whether the applied method of pneumatic pressure measurement could be used with patients in every day nursing and whether reliable and valid data could be generated from patients who have already developed bedsores. In order to answer these questions measurements were taken on 23/19 patients, including patients in lateral position, placing measuring instruments between the mattress/bed system and the body. The soft storage systems results prove a significant pressure reduction at all measuring points (p < 0.05), at the os coccygis even a highly significant pressure reduction (p < 0.01). The alternating pressure systems results show that the average maximum pressure over 12 min lies between 56.39 mmHg and 38.94 mmHg with differing amplitudes (75.47 mmHg-5 mmHg) and alternating frequency (1.5 min-10 min).

Humans↗

[Contrast enhanced power Doppler sonography: comparison of various administration forms of the ultrasound contrast agent Levovist].

PURPOSE: Objective of the present study was the comparison of various administration forms of the ultrasound contrast medium Levovist with regard to duration and intensity of contrast enhancement in patients with tumors of the liver or pancreas. PATIENTS AND METHODS: Seven patients with tumors of the liver or pancreas were examined prospectively using power Doppler sonography. Ultrasound contrast enhancement was achieved using Levovist (8 ml, 400 mg/ml) in three different administration forms: 1st as a bolus injection through the main channel, 2nd through the injection valve of an intravenous cannula, or 3rd as a continuous infusion. Semiquantitative evaluation of the degree of contrast enhancement over the course of the examination was conducted by three independent examiners. RESULTS: Levovist, administered by continuous infusion, resulted in a significantly longer average period of contrast enhancement (9:43 min (extratumoral), 7:34 min (intratumoral)) than did the same dosage administered as a bolus injection through the main channel (6:01 min (extratumoral), 4:54 min (intratumoral), p = 0.0156 (extratumoral); p = 0.0313 (intratumoral), but contrast intensity was decreased. Bolus injection through the injection valve of the i.v. cannula was associated with decreased duration and intensity of contrast enhancement compared with injection through the main channel. CONCLUSION: Compared with bolus injection, the continuous infusion of Levovist resulted in a significant prolongation of the duration but in a decreased intensity of contrast enhancement. Administration of Levovist through the injection valve does not result in optimal contrast enhancement and is therefore not recommended.

Adult↗

[The research situation in abdominal sonography in the gastroenterology departments of university hospitals in the Federal Republic of Germany].

Objective of the present study is to provide a current overview of the present state of research in abdominal ultrasound in the gastroenterological departments of university hospitals in Germany. We conducted a survey assessing the number of research projects in progress, sources of financial support, sponsorship by the private sector and publications generated. Reports from 28 of 35 gastroenterological departments responding to the survey indicated that a total of 124 research projects were in progress during the survey period, for an average of 3.5 projects per department. Clinical issues were addressed in 78 studies, technical questions in 33 studies and other questions in 13 studies. Of the 117 publications generated, 50 appeared in German-language journals and 67 in English-language journals. At present, neither the German Research Association (DFG) or the European Union (EU) is financially underwriting an ultrasound research project in the gastroenterological department of any German university hospital. Ultrasound remains the most frequently applied diagnostic imaging technique in gastroenterology. In order to convert the enormous technological progress into improved diagnostic capabilities, there must be a significant expansion in research support for gastrointestinal ultrasound.

Abdomen↗

Natural history of the growth of the hand: part II--hand length as a treatment guide in the pediatric trauma patient.

BACKGROUND: In a previous study, we defined the natural history of the growth of the hand. In particular, we demonstrated that the palmar aspect of the hand is approximately 0.78% of body surface area (BSA). We also demonstrated a relationship between the area of the palmar surface of the hand and the total BSA as growth proceeds. Seeking to improve the usefulness of hand size as a guide to predicting body size, we examined the length of the hand as a predictor of body mass and BSA. METHODS: Bilateral hand tracings were obtained from 800 volunteers ranging in age from 2 to 89 years. The hand tracings were measured, and the length and width of the hands were determined. The height and weight of each individual were measured, and his or her BSA was calculated. The data was subjected to statistical and graphical analyses. RESULTS: Hand length is an excellent predictor of BSA and body mass. Hand length as a predictor of body size is independent of the gender of the subject and most accurate for ages 2 to 17 years. The correlation is so highly predictive that it is possible to derive a treatment guide based on hand length. The length of the hand predicts body weight and BSA and can be used to predict baseline intravenous fluid requirements and the volume of packed red blood cells to be transfused to raise the hematocrit 3%. CONCLUSIONS: Hand length is a simple measurement that may be used as a treatment guide. Hand length will predict body weight and body surface area independently of the gender of the subject.

Adolescent↗