Need for improved outcome measures in pulmonary arterial hypertension related to systemic sclerosis.
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Biomedical subjects
Publications and source records attributed to F Behrens.
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Eye position and angular velocity were measured in squirrel monkeys (Saimiri sciureus) by means of the electromagnetic scleral search-coil technique. Horizontal sigma-optokinetic nystagmus (sigma-OKN) was elicited by a stationary, stroboscopically illuminated, periodic, vertical-stripe pattern lining a vertical cylinder. The relationship between the mean slow-phase eye angular velocity, Ve, of sigma-OKN and the product of pattern period, Ps, and flash frequency, f(s), was determined. When Ve approximated k x Ps x f(s) (deg x s(-1)) and k was an integer > or = 1, the sigma-paradigm was fulfilled. Sigma-OKN could be evoked in different "modes", whereby k approximated 1, 2,...n. The sigma-OKN properties of squirrel monkeys were similar to those measured for sigma-OKN in the "stare" mode in man, with the exception of a long-lasting optokinetic afternystagmus (sigma-OKAN) appearing in the monkey. A considerable amount of temporal variability in flash sequence intervals ("temporal noise"), causing retinal error signals that interfered with the sigma-paradigm, was accepted by the visuo-motor system without interruption of sigma-OKN. This observation was explained by the operation of a short memory device for perception of visual motion. The internal gain, g(i), which relates the retinal "error" displacement velocity, Vr, and Ve depended, in turn, on Vr according to a function resembling the known relationship between neuronal activity of NOT (nucleus of the optic tract) nerve cells and Vr. This observation may be taken as direct proof that sigma-OKN can be explained by a centrally preprogrammed relationship between the retinal velocity, Vr, and the OKN slow-phase eye velocity, Ve. It is stipulated that the sum of Vr and efference copy signals generated in cortical or subcortical gaze centers is the essential component controlling the perceived velocity of the sigma-movement, whereby a short-term integrator plays a role for squirrel monkey sigma-OKN. When the flash frequency, f(s), was modulated periodically according to a sinewave or "triangular" function at a rate below 0.5 cycles x s(-1), Ve was found to respond with a corresponding modulation, provided the modulation amplitude did not exceed 50% of the mean flash rate. When the latter occurred, nonlinear responses could be observed. A similar response was found when the speed of "real" optokinetic stimuli was varied sinusoidally. Under these experimental conditions, however, the amplitude of the Ve variation yielded up to 1.0 approximately linear responses.
BACKGROUND: Despite an increasing incidence, relatively few studies have examined the factors that predict morbidity and mortality in older patients and several reports have found standard predictors such as the Injury Severity Score to be less useful in this patient population. Similarly, the effect of skeletal injury has not been examined with regard to complications and mortality. The purpose of this study was to review a large multicenter experience with elderly trauma patients to isolate factors that might predict morbidity and mortality. The potential effect of skeletal long-bone injury was of particular interest. METHODS: The charts of all patients older than 60 years who were admitted to one of four Level I trauma centers after sustaining blunt trauma were reviewed. Mechanisms of injury included in the study were motor vehicle crash, pedestrian struck, fall from a height, and crush injury. Slip-and-fall injuries were excluded. A total of 326 patients met inclusion criteria. Variables studied included age, sex, mechanism of injury, Injury Severity Score (ISS), Revised Trauma Score, Glasgow Coma Scale (GCS) score, blood transfusion, fluid resuscitation, surgery performed (laparotomy, long-bone fracture stabilization, both), and timing of surgery. Outcome variables measured included incidence of adult respiratory distress syndrome, pneumonia, sepsis, myocardial infarction, deep venous thromboembolism, gastrointestinal complications, and death. chi2, logistic regression, t test, and nonparametric analyses were done as appropriate for the type of variable. RESULTS: The average age of the patients was 72.2+/-8 years. Overall, 59 patients (18.1%) died, of whom 52 of 59 survived at least 24 hours. Statistical significance for continuous variables (p < 0.05) using univariate analysis was reached for the following factors for the patients who died: higher ISS (33.1 vs. 16.4), lower GCS score (11.5 vs. 13.9), greater transfusion requirement (10.9 vs. 2.9 U), and more fluid infused (12.4 vs. 4.9 L). Logistic regression analysis was performed to determine the factors that predicted mortality. They included (odds ratios and p values in parentheses) transfusion (1.11, p = 0.01), ISS (1.04, p = 0.008), GCS score (0.87, p = 0.007), and fluid requirement (1.06, p = 0.06). Regarding surgery, orthopedic surgery alone had an odds ratio of 0.53, indicating that orthopedic patients was less likely to die than patients who did not undergo any surgery. Patients who underwent only a general surgical procedure were 2.5 times more likely to die (p = 0.03) and patients who underwent both general and orthopedic procedures were 1.5 times more likely to die (p = 0.32) than patients who did not require surgery. Early (< or =24 hours) versus late (>24 hours) surgery for bony stabilization did not have a statistical effect on mortality (11% early vs. 18% late). Two patients in need of bony stabilization, however, died before these procedures were performed. With regard to complications, regression analysis revealed that ISS predicted adult respiratory distress syndrome, pneumonia, sepsis, and gastrointestinal complications; fluid transfusion predicted myocardial infusion; and need for surgery and transfusion requirements predicted sepsis. These complications, in turn, were significant risk factors for mortality. This large series of elderly patients demonstrates that mortality correlates closely with ISS and is influenced by blood and fluid requirements and by GCS score. The institution-specific mortality was the same when adjusted for ISS. The need for orthopedic surgery and the timing of the surgery was not a risk factor for systemic complications or mortality in this series. CONCLUSION: Mortality is predicted by ISS and by complications in older patients. Seventy-seven percent of the orthopedic injuries were stabilized early, but the timing of surgery did not have any statistical effect on the incidence of complications or mortality. (ABSTRACT TRUNCA
Centromeres remain the least characterized regions of human chromosomes because they have a very high content of repetitive DNA. Here, we describe a microdissection library from the centromeric region of human chromosome 7 and its use for generating sequence tagged sites (STSs). The library contains about 1500 clones with an average insert size of 150 bp and only about 15% of the clones harbour repetitive human DNA. Seven clones hybridizing to alphoid DNA were found to correspond to a fragment of the D7Z2 alphoid array on chromosome 7, thus confirming the origin of the library. A number of clones not containing known repetitive DNA were used to generate STSs that identified yeast artificial chromosomes (YACs) and in turn allowed the STSs to be placed on the physical map. One STS is located between the two Genethon genetic markers closest to the centromere on the q side. Another STS was located 3-4cM away in 7q11.2, while a third identified YACs containing both low-copy and alphoid sequences that are not yet mapped but are clearly centromeric. The library therefore comprises a collection of sequences from the centromeric region of chromosome 7 that can be used to generate STSs and to map the entire centromeric region.
This retrospective trail was designed to evaluate the effectiveness and safety of femoral nailing on a radiolucent table with manual traction only. Eighty-three femoral shaft fractures treated by antegrade nailing were included in this study. Group 1 consisted of 24 femur fractures that were reduced and nailed with manual traction. Group 2 consisted of 59 femur fractures treated with the aid of a fracture table. There were 10 patients in Group 1 and 19 patients in Group 2 needing multiple procedures. In Group 1, significantly fewer redrapings and table transfers were necessary. There was no increase in operative time. There were no operative complications in Group 1 and there was 1 operative complication in Group 2--a radial nerve palsy. Postoperative malalignment was minimal in both groups. Intramedullary nailing of femoral shaft fractures on a radiolucent table using manual traction is associated with no increase in morbidity. It also facilitated quicker and more effective treatment of the patient with polytrauma. No undue risks or contraindications were identified; however, the help of an assistant was invaluable.
The optokinetic nystagmus is a phylogenetically old reflexive reaction of the eyes to the movements of the visual surroundings. Two components can be distinguished: (1) the direct one is considered to represent a cortically transmitted loop through the posterior parietal areas: MT and MST; (2) the indirect component passes through brain stem nuclei. One of them is the pretectal nucleus of the optic tract in which we found neurons related to the velocity of the moving pattern. Since in neurons of the oculomotor nuclei the neuronal activity is related to eye position, integration must take place somewhere in the circuit. The brain stern-mediated indirect component is influenced by the vestibular organs, not only by semicircular canals but also by otoliths.
Optimal temperature conditions for the detection of 28 known mutations on 15 exons of the human cystic fibrosis transmembrane conductance regulator gene by single strand conformation polymorphism analysis using the Diagen TGGE Apparatus were established. This procedure was applied to the detection of unknown mutations in 58 non-deltaF508 chromosomes. Three novel mutations, -471del3 (5' flanking region), 3171insC (exon 17a) and 4700(T)8/9 (3' non-translated region) of the CFTR gene were found. Mutation 3171insC occurred in conjunction with the delta F508 mutation on the other allele of a child presenting with severe pathology. Mutation -471del3 has so far only been found in one healthy individual and her father, and 4700(T)8/9 is a DNA sequence polymorphism.
A representative multicenter cystic fibrosis (CF) mutation analysis on about half of all known cystic fibrosis patients of the 5 East German Länder is reported. Analyses for 17 mutations, among them Delta F508, R553X, G542X, S549R,N,I, G551D, S1255X, R347P,H, and Y122X, were performed. As expected, the delta F508 mutation in exon 10 of the CFTR gene is the major gene alteration causing CF in our patients. However, in comparison to studies from Western Germany, a significantly lower percentage of just over 60% is found in our patients, resembling data obtained from slavonic populations. The severe phenotype of cystic fibrosis is most frequently associated with homozygosity for the delta F508 mutation. No particular allele association could be found with the intermediate and mild phenotypes of this disease. The next most frequent of the investigated mutations is R553X (13.3% of non-delta F chromosomes) followed by R347P (9.2%) and G542X (4.4%).
An algorithm is described to discriminate automatically between saccades and slow eye movements. Sampled data of the eye position have been used to calculate the momentary acceleration of the eye. The higher acceleration values of the saccadic eye movements as opposed to the slow compensatory or pursuit eye movements served to differentiate between the two. The method is demonstrated by search-coil data in squirrel monkeys.
The use of Ender nails for the treatment of femoral shaft fractures has been described as technically easier and less time consuming than current intramedullary nailing techniques. We reviewed our results with unlocked Ender nails in 26 stable and 17 unstable fracture patterns an average of 3-4 years after injury. Because of continued instability, 42% of the stable and 76% of the unstable groups required adjunctive stabilization in the form of skeletal traction, a cast, or an external fixator. Additionally, nail migration and shortening and loss of motion at the knee were seen in 14 fractures in each group. Although two thirds of the patients with stable fracture patterns obtained good or excellent results, no outcome in the unstable group was rated excellent and only 19% were considered good. We therefore recommend that rigid locked intramedullary nails be used in femoral diaphyseal injuries. The use of Ender nails should be limited to stable fracture patterns and locked with screws or wires. They may be particularly useful for fractures in femora with small medullary canals (less than or equal to 8 mm), fractures below noncemented femoral prostheses, and fractures in young children requiring intramedullary stabilization without injuring the physeal plates.
Superior dislocation of the proximal tibiofibular joint occurred in a 34-year-old woman who sustained a Grade 3B open left tibial fracture. An external fixator was applied to the tibia, and the tibiofibular joint was treated by closed reduction. Two bone graftings were performed, and the patient ultimately required a fibular osteotomy to allow tibial impaction. At 10 months posttrauma, the patient is fully weight-bearing and has no pain either at the tibia or the tibiofibular joint.
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Knees of mature dogs were immobilized for 6 weeks by long-leg casts allowing 8 degrees-15 degrees of motion, a model studied by others, or with external fixators, a new, more severe model that kept the joints rigid. Some animals were allowed to recover for 1 week after the immobilization period. Articular cartilage was examined histologically and biochemically. After 6 weeks of immobilization, water increased 7% in both casted and fixator-immobilized joints compared with normal knee cartilage, while hexuronic acid was 23 and 28% lower, respectively. The limited motion permitted by the casts resulted in a smaller depression of proteoglycan synthesis and less proteoglycan loss during immobilization than occurred in the rigid external fixator group. The protective effect of limited motion was shown clearly during the recovery period: as measured by hexuronic acid content, cartilage from the casted joints had almost recovered within 1 week, whereas the external fixator group experienced little or no recovery during the week after treatment. In contrast to previous studies by others with casted joints, both newly synthesized [35S]sulfate-labeled and accumulated unlabeled proteoglycans from both casted and fixator-immobilized cartilages were able to form complexes with exogenous hyaluronic acid to the same extent as those from control cartilage. Thus, in immobilized cartilage, failure of the newly synthesized proteoglycan to bind to hyaluronate is not a mechanism of accelerated proteoglycan loss. The accelerated proteoglycan turnover appears to be caused by a combination of decreased synthesis and increased proteolysis of the secreted proteoglycans.(ABSTRACT TRUNCATED AT 250 WORDS)
A method is described to calibrate the eye position signals measured by means of Robinson's electromagnetic scleral search-coil technique in animals which can barely fixate for calibration, e.g. squirrel monkeys, or not at all, e.g. rabbits. Electrical or magnetic interferences superimposed on the search-coil signal can be determined by this method. Consequently, the quality of offset compensation can be tested.