PlanHab study: assessment of psycho-neuroendocrine function in male subjects during 21 d of normobaric hypoxia and bed rest.

Immobilization and hypoxemia are conditions often seen in patients suffering from severe heart insufficiency or primary pulmonary diseases (e.g. fibrosis, emphysema). In future planned long-duration and exploration class space missions (including habitats on the moon and Mars), healthy individuals will encounter such a combination of reduced physical activity and oxygen tension by way of technical reasons and the reduced gravitational forces. These overall unconventional extraterrestrial conditions can result in yet unknown consequences for the regulation of stress-permissive, psycho-neuroendocrine responses, which warrant appropriate measures in order to mitigate foreseeable risks. The Planetary Habitat Simulation Study (PlanHab) investigated these two space-related conditions: bed rest as model of reduced gravity and normobaric hypoxia, with the aim of examining their influence on psycho-neuroendocrine responses. We hypothesized that both conditions independently increase measures of psychological stress and enhance neuroendocrine markers of stress, and that these effects would be exacerbated by combined treatment. The cross-over study composed of three interventions (NBR, normobaric normoxic horizontal bed rest; HBR, normobaric hypoxic horizontal bed rest; HAMB, normobaric hypoxic ambulatory confinement) with 14 male subjects during three sequential campaigns separated by 4 months. The psychological state was determined through three questionnaires and principal neuroendocrine responses were evaluated by measuring cortisol in saliva, catecholamine in urine, and endocannabinoids in blood. The results revealed no effects after 3 weeks of normobaric hypoxia on psycho-neuroendocrine responses. Conversely, bed rest induced neuroendocrine alterations that were not influenced by hypoxia.

Role of vacancies in metal-insulator transitions of crystalline phase-change materials.

The study of metal-insulator transitions (MITs) in crystalline solids is a subject of paramount importance, both from the fundamental point of view and for its relevance to the transport properties of materials. Recently, a MIT governed by disorder was observed in crystalline phase-change materials. Here we report on calculations employing density functional theory, which identify the microscopic mechanism that localizes the wavefunctions and is driving this transition. We show that, in the insulating phase, the electronic states responsible for charge transport are localized inside regions having large vacancy concentrations. The transition to the metallic state is driven by the dissolution of these vacancy clusters and the formation of ordered vacancy layers. These results provide important insights on controlling the wavefunction localization, which should help to develop conceptually new devices based on multiple resistance states.

Perioperative blood conservation strategies for pediatric scoliosis surgery.

PURPOSE: Many pediatric patients with severe scoliosis requiring surgery have baseline anemia. Pediatric scoliosis fusion surgery is associated with perioperative blood loss requiring transfusion. As such, many patients in this surgical population could benefit from a perioperative blood conservation program. METHODS: Here we present a narrative review of perioperative blood conservation strategies for pediatric scoliosis surgery involving nurses, transfusion medicine physicians, anesthesiologists, surgeons, dieticians, perfusionists and neurophysiologists spanning the pre-, intra- and postoperative phases of care. RESULTS: The review highlights how perioperative blood conservation strategies, have the potential to minimize exposures to exogenous blood products. Further, we describe a relevant example of blood conservation related to the care of a Jehovah's Witness patient undergoing staged scoliosis repair. Lastly, we outline areas which would benefit from clinical studies to further elucidate perioperative blood conservation interventions and their outcomes relevant to pediatric scoliosis surgery patients. CONCLUSION: Interdisciplinary communication and meticulous blood conservation strategies are proving to be a means of reducing if not eliminating the need for allogeneic blood products for surgical correction of pediatric scoliosis.

[Preclinical evaluation of coated knee implants for allergic patients]. / Präklinische Ergebnisse beschichteter Knieimplantate für Allergiker.

BACKGROUND: 10-15% of the population show allergic reactions against skin contact to metals as nickel, cobalt or chromium and have thus a risk of not tolerating implants containing those materials. The relationship between periimplantary hypersensivity reaction and given cutaneous contact allergy is currently unknown. A new developed multilayer coating system is supposed to prevent long-term allergic reactions that may result from uncoated implants. METHODS: Stability and function (concerning bonding durability, wear and ion release to the serum) of the multilayer coating system has been examined in a test series. RESULTS: The specific architecture of the multilayer coating system evidences a very good bonding durability. The results of the test in the simulator show a reduction of wear of approximately 60% compared to the uncoated implants. Ion concentrations within the serum of the wear tests were by magnitudes lower than those measured in reference tests on uncoated components. CONCLUSION: The results of the preclinical evaluation prove that the durability and function of the multilayer coating system are as intended.

Changes in soft tissue composition are the primary predictors of 4-year bone mineral density changes in postmenopausal women.

UNLABELLED: Changes in body weight influence bone mineral density, but the role of body composition is not clear in postmenopausal women. Body weight and soft tissue composition predicted bone changes independent of calcium supplementation and exercise frequency, indicating that soft tissue composition should be measured in clinical trials. INTRODUCTION: The purpose of this study was to examine the relationship between changes in body weight and composition and changes in 4-year bone mineral density (BMD) after accounting for age, 4-year exercise frequency (EX), and 4-year calcium supplement intake (CA) in postmenopausal women with and without hormone therapy (HT). METHODS: Postmenopausal women (aged 40-65 years) either using HT (for 1-3.9 years) or not using HT (for > or =1 year) were recruited to the study. EX and CA was monitored throughout the study and 167 women completed 4 years. BMD and soft tissue composition measurements were made using dual-energy X-ray absorptiometry. Regression was used to predict 4-year BMD changes from EX, CA, age, baseline and 4-year changes in body weight and composition. HT users (n = 115, 55.3 +/- 4.3 years) and non-users (n = 52, 57.5 +/- 4.7 years) were analyzed separately. RESULTS: The models predicting regional BMD changes that included soft tissue composition changes explained the most variation compared with those with body weight or EX and CA alone. Larger amounts of variation in BMD changes were explained in the no HT group. CONCLUSION: Body composition changes are important positive predictors of BMD changes independent of EX and CA supplementation, but their contribution varies according to bone site and with HT use.

Nuclear exclusion of transcription factor IIIA and the 42s particle transfer RNA-binding protein in Xenopus oocytes: a possible mechanism for gene control?

The intracellular location of 7S and 42S RNP particles in Xenopus oocytes has been determined by immunohistochemistry. Using antibodies directed against the 48-mol-wt protein component of the 42S particle and against transcription factor IIIA, the protein moiety of the 7S particle, we show that these ribonucleoprotein particles are detectable only in the oocyte cytoplasm, being excluded from the nucleus. The mechanism of this nuclear exclusion, and its possible significance in the regulation of 5S RNA gene expression, are discussed.

PlanHab Study: Consequences of combined normobaric hypoxia and bed rest on adenosine kinetics.

Adenosine plays a role in the energy supply of cells and provokes differential, hormone-like functions in circulating cells and various tissues. Its release is importantly regulated by oxygen tension. This renders adenosine and its kinetics interesting to investigate in humans subjected to low oxygen conditions. Especially for space exploration scenarios, hypoxic conditions - together with reduced gravity - represent two foreseen living conditions when planning manned long-duration space missions or planetary habitats. The PlanHab study investigated microgravity through inactivity in bed rest and normobaric hypoxia to examine their independent or combined effect on adenosine and its kinetics. Healthy male subjects (n = 14) completed three 21-day interventions: hypoxic bed rest (HBR); hypoxic ambulatory confinement (HAMB); normoxic bed rest (NBR). The interventions were separated by 4 months. Our hypothesis of a hypoxia-triggered increase in adenosine was confirmed in HAMB but unexpectedly also in NBR. However, the highest adenosine levels were noted following HBR. Furthermore, the percentage of hemolysis was elevated in HBR whereas endothelial integrity markers stayed low in all three interventions. In summary, these data suggest that neocytolysis accounts for these effects while we could reduce evidence for microcirculatory changes.

The cytomegalovirus enhancer: a pan-active control element in transgenic mice.

In an effort to identify widely active positive regulatory elements, we have examined the action of the cytomegalovirus enhancer-promoter in transgenic mice. These elements activated expression in 24 of 28 tissues tested. The greatest expression was observed in the heart, kidney, brain, and testis. Maximum expression further localized to specific cells within the heart and kidney.

Factors influencing nurses' judgements about self-neglect cases.

From the perspective of the practising nurse self-neglect may best be understood in terms of a set of complex and often poorly defined clinical problems in which two key clinical issues are "how do I judge whether this person has the capacity to make decisions about their lifestyle?" and "do we need to treat this person using mental health legislation?" These are taxing questions as judging if a patient has the capacity to make decisions about their lifestyle choices is difficult for even the most experienced clinicians. Such determinations require nurses to form a judgement as to mental capacity of the patient. We do not know what patient characteristics and in what combination nurses use these when making these judgements. This factorial survey aimed to identify which patient characteristics influenced Registered Nurses' judgements on decision-making capacity and decisions on the use of interventions which require statutory interventions in cases of self-neglect. Judgements on decision-making capacity were overwhelmingly predicted by information of the patients' mental health status. Nurses place patients in one of three broad categories of no mental illness, minor mental illness and severe mental illness. This categorization appears to operate as a fast and frugal heuristic indicating that nurses may use mental status as a cognitive screen to work from in judging self-neglect. Although there is a correlation between the severity of mental illness and the capacity for making decisions they are not the same. This study shows the continued work that needs done in educating nurses not only about self-neglect but also about the role a patient's mental status may have in assessment of problems.

[Orthopedic treatment of spinal deformities in infancy and early childhood]. / Le traitement orthopédique dans la pathologie vertébrale du petit enfant.

Surgical treatment of spinal deformities in infancy and early childhood (before age 6) is often very useful if the lesion is localized and curable by one unique surgery, such as hemivertebra resection and fusion. On the contrary, if the lesion, whether idiopathic or paralytic, is extended to a large part of the spine, early surgical treatment in infancy gives very disappointing results and often worsens the status of the child, especially respiratory function if the lesion is mainly thoracic. The goal of this paper is to explain in detail indications and management of non-surgical treatment of such lesions. These are variable according to localization, etiology, and associated anomalies, and are mainly based on proper casting (often repeated), bracing (often intermittent between casting) and proper respiratory equipment. From time to time, a surgical treatment is locally indicated, but most of the time results are disappointing and the best is to repeat non-surgical treatment until proper definitive arthrodesis can be performed. This approach is not very rewarding for the child and family, but is clearly better than sudden extensive surgery in early childhood with very severe and disastrous results in adulthood. It is our hope that the recommendations and thoughts presented in this paper will help readers to manage young children using the most efficient, non-aggressive, but long-lasting therapy.

A GR-motif functions in nuclear accumulation of the large FGF-2 isoforms and interferes with mitogenic signalling.

Nuclear translocation has been documented for members of the fibroblast growth factor (FGF) family in addition to their roles as extra-cellular signalling molecules. Fusing different parts of the chicken FGF-2 open reading frame to pyruvate kinase shows that direct nuclear accumulation is mediated by the amino-termini of the two leucine initiated FGF-2 isoforms (Leu-isoforms; 21.5 and 20.0 kDa). An evolutionarily conserved glycine-arginine (GR)-motif is present in the 21.5 kDa Leu-isoform and a shorter GR-repeat in the 20.0 kDa Leu-isoform, whereas no such repeats are present in the 18.5 kDa FGF-2 isoform (Met-isoform). Expression in NIH3T3 fibroblasts shows that the 21.5 kDa Leu-isoform is predominantly nuclear, whereas the Met-isoform is predominantly cytoplasmic. Most importantly, insertion of the GR-motif into the Met-isoform results in a protein with characteristics similar to the Leu-isoforms, as shown by nuclear accumulation of the chimeric MGR-protein. Furthermore, only NIH3T3 fibroblasts expressing the Met-isoform proliferate under serum starvation conditions, whereas cells expressing either the MGR- or Leu-isoforms stay growth arrested. These studies show that the GR-signal mediates nuclear translocation of endogenous Leu-isoforms and blocks their mitogenic activity.

Nucleo-cytoplasmic translocation and secretion of fibroblast growth factor-2 during avian gastrulation.

The expression and distribution of the fibroblast growth factor-2 (FGF-2 or bFGF) proteins during early avian embryogenesis has been analysed in detail. Three FGF-2 protein isoforms of 18.5, 20.0 and 21.5 kDa are expressed during gastrulation of chicken embryos. Using whole mount immunohistochemistry, these proteins were found to be predominantly nuclear in prestreak blastodiscs during mesoderm induction. Distribution of positive cells in the epiblast was mosaic, whereas all cells of the forming hypoblast expressed the FGF-2 proteins. During primitive streak formation, the proteins started to translocate to the cytoplasm in epiblast cells but remained nuclear in the hypoblast. The FGF-2 proteins became predominantly cytoplasmic in all cells during the subsequent developmental stages. Their highest levels were detected in endodermal cells underlying Hensen's node and the newly formed notochord, the dorsal apex of all epiblast cells and, most interestingly, in the extra-cellular basal lamina separating the epiblast from newly formed mesoderm. Heparin and suramin treatment of these advanced embryos (stage 4) revealed a dose-dependent inhibition on the regression of Hensen's node and formation of mesodermal derivatives such as somites. The results are discussed with respect to current models on FGF-mediated functions during vertebrate mesoderm induction and regionalization.

Ectopic expression of genes during chicken limb pattern formation using replication defective retroviral vectors.

A gene transfer method to ectopically express genes during chicken limb pattern formation using replication defective retroviral vectors has been established. Spherical non-proliferating (mitomycin C treated) aggregates of clonal retrovirus producing cells were grafted directly into developing chicken wing buds. The cell aggregates had to be placed in direct contact with the highly proliferative cells of the wing bud to promote efficient in vivo infection of embryonic cells by the released retroviral particles. The majority of grafts resulted in widespread expression of a reporter gene (encoding bacterial beta-galactosidase) during limb pattern formation and early limb bud outgrowth without affecting morphogenesis. This method provides a novel approach to study the effects of ectopic gene expression on limb pattern formation. Possible future applications to study other developmental processes are discussed.

Vascular malformations of the pons in children.

Three children reported here and an additional five patients from the literature with angiomas of the pons had a total of 19 clinical episodes of neurologic "illness." Thirteen of these episodes were ictal and six were progressive in onset. The progressive onset was identical with that occurring in patients with tumors of the brain stem. Laboratory and radiographic studies were not uniformly helpful in differentiating this disorder from the more common brain-stem glioma. The survival of these patients varies from several hours to 15 years.

Eastern equine encephalomyelitis. Histopathologic and ultrastructural changes with isolation of the virus in a human case.

Enveloped Toga virus particles were demonstrated by means of an electron microscopy in the brain tissues of a 3-year-old girl with acute encephalitis. Areas of demyelinization and necrosis throughout the white matter and brainstem were revealed by light microscopy. These viral particles were identified as eastern equine encephalomyelitis virus in postmortem isolation of the virus utilizing young mice and complement-fixation studies. To the authors' knowledge, this is the first demonstration of eastern equine encephalomyelitis virus particles in human tissues by electron microscopy.

Progressive rotational dislocation in kyphoscoliotic deformities: presentation and treatment.

STUDY DESIGN: Progressive rotational dislocation of the spine has been described as the most serious evolutive risk of kyphoscoliosis. A retrospective chart review was conducted on 11 patients with this deformity. OBJECTIVES: To delineate the clinical and radiologic characteristics of this entity to facilitate early diagnosis and treatment. The outcome after treatment was analyzed to point out the rationale for appropriate treatment. METHODS: The characteristic radiologic feature was a short sharp angled kyphosis (average 112) at the junction of two lordoscoliotic curvatures. The etiology of the spinal deformity was neurofibromatosis in four patients and various dysplastic conditions in seven patients. Two patients had congenital vertebral defects. Structural weakness of the bone was therefore a basic feature. Neurologic impairment was identified in three patients (one complete, two incomplete). Four patients had a nonunion after a previous attempt at spinal fusion: two after a combined anterior and posterior fusion with an anterior approach from the convexity and two after a posterior fusion alone. All patients underwent complete circumferential stabilization through anterior strut-grafting and posterior fusion. An anterior approach from the concavity was performed systematically with tibial strut grafts inserted in a palisade fashion. Preoperative correction of the deformity was performed by progressive controlled elongation in a Stagnara elongation cast. Cotrel-Dubousset instrumentation was used in two patients, Harrington instrumentation was used in two patients, and cast immobilization alone was used in seven patients. RESULTS: The average follow-up period was 5 years 5 months. All but one patient achieved successful spinal fusion. Loss of correction at the latest follow-up evaluation was less than 3 degrees in nine patients. The two patients with incomplete neurologic deficits were improved, but the patient with the complete deficit remained unchanged after surgery. CONCLUSIONS: Awareness of the possibility of a progressive rotational dislocation in dystrophic forms of kyphoscoliosis should allow for an early diagnosis and stabilization. The percentage of patients having a neurologic deficit in this series was significantly less important than in the initial report. Early anterior strut grafting from the concavity of the scoliotic curvature and posterior fusion is recommended.

The congenital dislocated spine.

STUDY DESIGN: The congenital dislocated spine has been defined as the potentially most serious form of congenital kyphosis with an abrupt single-level displacement of the spinal canal. A retrospective chart review was conducted on 19 patients with this deformity. OBJECTIVES: To delineate the clinical and radiologic characteristics of this entity, and to analyze the outcome after treatment. SUMMARY OF BACKGROUND DATA: An anterior failure of formation was the basic feature. Kyphosis was variable. Vertebral displacement in the frontal plane was present in seven patients, and sagittal displacement was constant. Mechanical instability was seen in 17 patients. Neurologic impairment was identified in 12 patients, and congenital paraplegia was seen in eight patients. An acute paraplegia occurred after minor trauma in one patient. METHODS: Seventeen patients were treated surgically. Thirteen patients underwent complete circumferential stabilization through anterior strut grafting and posterior fusion without instrumentation, usually before age 3 years. Neurosurgical decompression was done in four patients. RESULTS: The average follow-up period was 8 years, 6 months. Nonunion of the posterior fusion mass was detected and successfully treated in five patients. A solid fusion seemed to be obtained in all patients at last follow-up evaluation. The neurologic status after neurosurgical decompression remained unchanged in three patients and was improved temporarily in one patient. CONCLUSIONS: Avoidance of neurologic morbidity requires early diagnosis and stabilization. The authors recommend early anterior strut grafting and posterior fusion. Exploration of the posterior fusion mass should be done systematically.

Posterior spinal fusion in neuromuscular scoliosis using a tibial strut graft. Results of a long-term follow-up.

STUDY DESIGN: Risks and benefits of using a tibial graft for posterior spinal fusion in neuromuscular scoliosis were evaluated in a long-term follow-up study. A consecutive series of 72 patients underwent posterior spinal fusion for neuromuscular scoliosis. OBJECTIVES: Radiologic outcome was assessed to evaluate the quality of the spinal fusion. Patients were followed serially to detect donor site complications. Mean follow-up was 17 years and 8 months (minimum: 6 years, 6 months). SUMMARY OF BACKGROUND DATA: Mean age of the patients at the time of surgery was 15 years. Progression of the curvature was minimal at last follow-up (mean progression at last follow-up: lumbar curve, 4.5 degrees; thoracic curve, 5.3 degrees). Concerning donor site complications, four patients had a leg length discrepancy of less than 2 cm at last follow-up. This complication was related to tibial overgrowth at the donor site. METHODS: Solid fusion was defined in this long-term study as the absence of modification of the radiologic aspect at last follow-up in addition to the presence of a massive contagious trabecular fusion mass. RESULTS: The fusion appeared to be solid in all patients. No obvious pseudarthrosis could be documented. The constant successful outcome differs significantly from spinal fusion that uses bank bone. The absence of stress fracture was correlated to the low level of constraint in this essentially nonambulatory population. CONCLUSION: This experience indicates that the tibial graft deserves consideration in posterior spinal fusion for neuromuscular scoliosis.

Iliosacral screw fixation for pelvic obliquity in neuromuscular scoliosis. A long-term follow-up study.

STUDY DESIGN: This was a retrospective review of a consecutive series of patients with neuromuscular spinal deformity who underwent posterior fusion and pelvic fixation using a long construct and an iliosacral screw. OBJECTIVES: To evaluate the risks and benefits of iliosacral screw fixation. SUMMARY OF BACKGROUND DATA: Neuromuscular scoliosis with pelvic obliquity poses one of the most challenging instrumentation problems, mainly because of the poor bone quality frequently found within the sacrum. Complications include failure of instrumentation, loss of sacral fixation, loss of lumbar lordosis, and a high rate of nonunion. METHODS: One hundred fifty-four patients with neuromuscular scoliosis and pelvic obliquity underwent posterior arthrodesis with pelvic fixation using an iliosacral screw. Anteroposterior scoliosis Cobb angle, frontal pelvic obliquity, and sacral inclination angle were measured before surgery, immediately after surgery, and at the 5-year and 3-month follow-up examination. Influence of etiology, severity of deformity, and associated anterior release at the scoliotic curve above also were assessed. RESULTS: Correction of scoliosis Cobb angle ranged from 53% to 70%, and loss of correction ranged from 3% to 14% at the last follow-up examination. Correction of pelvic obliquity ranged from 60% to 84%, and loss of correction was mild. Sacral inclination angle approached normal values in all patients, except for those with myelomeningocele who had preoperative pelvic retroversion. Loss of correction ranged from 0.3 degree to 5.4 degrees at the last follow-up examination. Complications and loss of correction mostly were encountered in patients with myelomeningocele and spinal muscular atrophy. CONCLUSIONS: Iliosacral screw fixation in neuromuscular scoliosis is technically standardized and easy and offers mechanically efficient and stable fixation.

Perthes' disease after the age of twelve years. Role of the remaining growth.

In order to define the prognostic factors in Perthes' disease in children older than 12 years, we reviewed 15 patients at the end of growth who were aged 12.1 to 14 years at presentation. The patients with the worst long-term prognosis (Stulberg class V) were compared with the others for age, skeletal maturity and remaining growth (Oxford method), as well as Catterall and Waldenström classifications at presentation. A significant difference (p = 0.001) was found for remaining growth (25% in Stulberg class V and 35% in the others) and also for the results at the end of growth when the remaining growth was over 30%, since this allowed sufficient time for reformation and remodelling of the femoral head.