Cervical spine arthrodesis in rheumatoid arthritis: a long-term follow-up.

Forty-one patients with rheumatoid arthritis involving the cervical spine had a posterior cervical arthrodesis. They were followed for a minimum period of seven years. The diagnoses prior to surgery included cranial settling, atlantoaxial subluxation, subaxial subluxation, and any combination of these three. All patients had posterior arthrodesis, with or without methylmethacrylate, and iliac crest autogenous bone graft. In addition, one patient had an anterior vertebrectomy, and two had transoral resection of the odontoid. Follow-up consisted of a subjective questionnaire, standard radiographs, and physical examination, including a neurologic exam. This information was compared to preoperative data available in the patient''s medical record, postoperative data, and the information obtained in a similar study undertaken in 1987. At the time of follow-up, thirteen patients were known to be dead. One patient could not be located. Of the remaining twenty-six patients, eighteen underwent the full examination, including physical exam and radiographs. The remaining nine patients were contacted and interviewed, but were unavailable for exam and radiographs. All patients considered the operation a success. Only one patient at follow-up had a non-union. This was stable over time. No patient had a deterioration in neurologic function. There was no significant degeneration or instability seen at levels adjacent to the fused segments as compared to the rest of the cervical spine. Posterior cervical spine arthrodesis for rheumatoid involvement of the neck is a safe, efficacious procedure with no significant deterioration of effects over time.     

EFFECTS OF DARKNESS AND OF STREPTOMYCIN ON THE FINE STRUCTURE OF EUGLENA GRACILIS

Siegesmund , Kenneth A., Walter G. Rosen , and Stanley R. Gawlik . (Marquette (J., Milwaukee, Wis.) Effects of darkness and of streptomycin on the fine structure of Euglena gracilis. Amer. Jour. Bot. 49 (2) : 137–145. Illus. 1962.—Dark-grown Euglena gracilis cells, transferred from streptomycin (SM)-containing medium to SM-free medium 5 days before transfer to light, turn green normally, indicating that proplastids are unaffected by SM. SM-bleached cells, grown in light, contain numerous bodies composed of concentric lamellae (CL bodies). These differ from chloroplasts in that their lamellae lack electron-dense dots, are not coalesced, and they lack a 3-layered limiting membrane and pyrenoids. CL bodies are absent from dark-grown normal and dark-grown SM-bleached cells, as well as from light-grown normal cells. It is suggested that CL bodies result from a derangement of chloroplast synthesis caused by SM blockage of chlorophyll synthesis.     

Reduction in subluxation and improved muscle function of the hemiplegic shoulder joint after therapeutic electrical stimulation.

Seventeen hemiplegic patients with chronic shoulder subluxation secondary to a cerebrovascular accident (CVA) were divided into three groups, two of which were subjected to 6 weeks of therapeutic electrical stimulation (TES) for 15 minutes twice a day, in order to assess the effectiveness of the treatment in reducing subluxation, and in improving shoulder abduction function. The third group was used as a control (C group). After 6 weeks of electrical stimulation of the supraspinatus (S group) and deltoid (D group), a significant (p<0.05) reduction in subluxation was observed in both groups when compared to the C group. The maximal force of shoulder abduction showed a tendency to increase in the S group (p<0.10). A significant increase in maximal force was also observed in the D group. In most of the TES-treated muscles, the interference pattern of EMG at maximum voluntary contraction increased. The amplitude of the EMG activity of the stimulated muscle also increased. Thus, we concluded that electrical stimulation therapy of the supraspinatus and the deltoid muscle is an effective treatment modality for shoulder subluxation and shoulder abduction function in hemiplegic patients.     

Rheumatoid Arthritis—Atlanto-Axial Subluxation and Its Clinical Presentation

The clinical picture, radiological findings and treatment of 22 patients with atlantoaxial subluxation and rheumatoid arthritis are described. This lesion, untreated, may result in damage to the spinal cord, paresis or sudden death. Occipital headache, present in 13 of 22 patients, was often aggravated by working with the head in forward flexion. Paresthesias were present in six patients. The spine of the axis was often prominent. In three patients there was objective evidence of cord compression with sensory and/or pyramidal signs. In eight the lesion was asymptomatic and discovered by routine lateral radiography in flexion, the position of maximum subluxation.Conservative treatment involved the continuous use of a cervical collar to limit neck flexion. This usually relieved subjective symptoms including headaches. Successful surgical fixation was performed in two individuals. Surgical indications included acute or chronic cord compression or severe symptoms unrelieved by a collar.     

Analysis of disordered muscle contractile function by assessments of the degree of potentiation of evoked mechanical response of the muscle

A study was made of the evoked mechanical response of the adductor under supramaximal stimulation of the ulnar nerve in 24 normal test subjects, 10 patients with the involvement of motoneurons and their axons, 30 patients with chronic derangement of the neuromuscular transmission (myasthenia) and 8 patients with hypothyrosis. A reverse dependence was found of the Pt/Po ratio on the magnitude of post-tetanic potentiation in all the examined. The capacity of the muscle to potentiate the tension in response to the double stimulus and during the post-tetanic periods inversely related to the initial amplitude of the evoked mechanical response of the muscle and the time of the muscle contraction. It is assumed that the universal mechanism of the regulation of muscle contractile function in health and disease underlies the regularities described.     

Treatment of sulphur mustard skin injury

Since its first use in 1917, sulphur mustard (SM) has been used virtually exclusively as a weapon of war. SM is a volatile liquid that damages any tissue it contacts as a vapour or liquid. SM primarily damages the skin, eyes and lungs producing massive inflammation culminating in the characteristic blistering of the skin which classifies SM as a vesicant. Several mechanisms of action at the cellular level have been proposed for SM, but none has ever been convincingly linked to the production of blisters or vesication. First aid for those contaminated with liquid SM consists of the rapid removal (within a few minutes) of liquid from the surface of the skin, as once penetrated into the stratum corneum it is very difficult to remove. In the absence of a mechanistically based specific therapy, SM skin injury is normally treated in a similar way to thermal and chemical burns, which it resembles pathologically. Effective therapy consist of treating the inflammation and where necessary removal of the dead eschar to facilitate healing. Post surgical care comprises the use of one of a number of available dressings used in thermal burn care and antibiotic creams should infection be present.     

Sphingomyelin Patches on Pancreatic Beta-cells Are Indicative of Insulin Secretory Capacity

The establishment and validation of specific markers on the surfaces of pancreatic beta-cells would have a significant impact on the development of agents that specifically target these cells for imaging and/or image-guided therapy in diabetes patient samples. We have recently described unique, cholesterol-stabilized sphingomyelin (SM) patches on the surfaces of beta-cells using the IC2 antibody. To further investigate the utility of SM patches as a unique beta-cell biomarker, we embarked on the current study to correlate the expression of this antigen with the insulin secretory capacity of beta-cells in tissue samples from patients and animals with type 1 and type 2 diabetes and compared this with samples from normal subjects. We found that the locations of SM patches were consistent with the insulin status of islets in all tissues studied. Using immunohistochemistry and staining with an IC2 antibody, we demonstrated a direct correlation between the reduced expression of SM patches and insulin production in diabetic individuals, indicating that the former could potentially serve as a functional biomarker of beta-cells. We believe that our results have significant implications for the further development of ligands with SM specificity for the non-invasive functional assessment of beta-cells and/or for targeted therapeutic delivery in diabetic patients.     

Changes of membrane phospholipid composition of human erythrocytes in hyperlipidemias. I. Increased phosphatidylcholine and reduced sphingomyelin in patients with elevated levels of triacylglycerol-rich lipoproteins.

The composition of red blood cell membrane and plasma phospholipids has been analyzed in patients with hyperlipidemias. In red cells of patients with elevated levels of triacylglycerol-rich lipoproteins, phosphatidylcholine (PC) was raised and sphingomyelin (SM) reduced, resulting in a 20% increase of the membrane PC/SM ratio. In plasma phospholipids of these patients PC and SM levels were also higher and lower, respectively and the plasma PC/SM ratio was elevated by more than 50%. Close positive correlations between plasma and membrane phospholipids were obtained for PC, SM and the PC/SM ratio in normolipidemic and hyperlipidemic donors. Plasmalogen phosphatidylethanolamine (PE), a supposed endogenous protector against lipid oxidation, was reduced by about 20% in red cell membrane lipids in hyperlipidemic patients. Also plasmalogen-PE in plasma tended to be reduced in hyperlipidemic donors. Plasma HDL levels were positively related to the content of plasmalogen PE in the red cell membrane. In conclusion, there are closely related increases in PC/SM ratios in plasma and the red cell membrane in patients with elevated levels of triacylglycerol-rich lipoproteins. It is speculated that decreases in red cell membrane plasmalogen-PE in hyperlipidemic patients could be related to impaired antioxidant protection, possibly as a consequence of reductions in plasma HDL levels.     

Experimentally induced neck pain causes a decrease in thoracic but not lumbar spine stability

Maintenance of spine stability is considered to be a critical component of spine health. Ross et al. (2015) used a topical capsaicin/heat pain sensitization model to experimentally induce lower back pain, and demonstrated that the experimental pain experience caused a decrease in the muscular contribution to lumbar spine rotational stiffness (related to mechanical stability) as well as lower back local dynamic stability (LDS). It has yet to be established if pain elsewhere in the body, specifically in other regions of the spine, can similarly affect the stability of the lower back. The purpose of this investigation was therefore to quantify thoracic and lumbar spine LDS as well as the muscular contribution to lumbar spine rotational stiffness after an experimental neck pain protocol. Results demonstrated that LDS of the thoracic spine decreased in response to the capsaicin/heat induced neck pain. Limited adaptation was required at the lumbar spine as demonstrated by the lack of statistically significant changes in lower back LDS or rotational stiffness.     

Cytogenetic effects of chemotherapy with three combinations of anti-tubercular drugs involving isoniazid,thiacetazone, para-aminosalicylic acid and streptomycin on human lymphocytes: chromosome aberrations,sister chromatid exchanges and mitotic index

Cytogenetic effects of three combinations of anti-tubercular drugs were evaluated on human lymphocytes in vivo and were compared with controls of two types: (1) newly diagnosed tuberculosis patients before starting therapy and (2) individuals from the general population. The drugs used were: isoniazid (INH), thiacetazone (TAZ), para-aminosalicylic acid (PAS), and streptomycin (SM). These drugs were tested in the following combinations: (a) INH + TAZ + SM, (b) INH + PAS + SM, (c) INH + SM. The frequency of chromosome aberrations was significantly increased in patients treated with both the triple drug combinations, i.e., with INH + TAZ + SM and INH + PAS + SM, whereas patients treated with INH + SM did not exhibit an increase in the frequency of chromosome aberrations as compared to the controls. Although both the triple drug combinations were clastogenic, none of the three drug combinations tested induced an increase in the frequency of sister chromatid exchanges (SCEs). In other words, the mechanisms leading to SCEs and chromosome aberrations may be different. SM appeared to depress the mitotic index in patients treated with INH + SM and INH + PAS + SM, though it was found to possess a mild anti-clastogenic effect. INH + TAZ + SM, on the other hand, enhanced the mitotic index. This enhanced mitotic index was probably due to the presence of TAZ.     

Making change last: applying the NHS institute for innovation and improvement sustainability model to healthcare improvement

The implementation of evidence-based treatments to deliver high-quality care is essential to meet the healthcare demands of aging populations. However, the sustainable application of recommended practice is difficult to achieve and variable outcomes well recognised. The NHS Institute for Innovation and Improvement Sustainability Model (SM) was designed to help healthcare teams recognise determinants of sustainability and take action to embed new practice in routine care. This article describes a formative evaluation of the application of the SM by the National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care for Northwest London (CLAHRC NWL).Data from project teams’ responses to the SM and formal reviews was used to assess acceptability of the SM and the extent to which it prompted teams to take action. Projects were classified as ‘engaged,’ ‘partially engaged’ and ‘non-engaged.’ Quarterly survey feedback data was used to explore reasons for variation in engagement. Score patterns were compared against formal review data and a ‘diversity of opinion’ measure was derived to assess response variance over time.Of the 19 teams, six were categorized as ‘engaged,’ six ‘partially engaged,’ and seven as ‘non-engaged.’ Twelve teams found the model acceptable to some extent. Diversity of opinion reduced over time. A minority of teams used the SM consistently to take action to promote sustainability but for the majority SM use was sporadic. Feedback from some team members indicates difficulty in understanding and applying the model and negative views regarding its usefulness.The SM is an important attempt to enable teams to systematically consider determinants of sustainability, provide timely data to assess progress, and prompt action to create conditions for sustained practice. Tools such as these need to be tested in healthcare settings to assess strengths and weaknesses and findings disseminated to aid development. This study indicates the SM provides a potentially useful approach to measuring teams’ views on the likelihood of sustainability and prompting action. Securing engagement of teams with the SM was challenging and redesign of elements may need to be considered. Capacity building and facilitation appears necessary for teams to effectively deploy the SM.     

Uniaxial mechanical strain modulates the differentiation of neural crest stem cells into smooth muscle lineage on micropatterned surfaces

Neural crest stem cells (NCSCs) play an important role in the development and represent a valuable cell source for tissue engineering. However, how mechanical factors in vivo regulate NCSC differentiation is not understood. Here NCSCs were derived from induced pluripotent stem cells and used as a model to determine whether vascular mechanical strain modulates the differentiation of NCSCs into smooth muscle (SM) lineage. NCSCs were cultured on micropatterned membranes to mimic the organization of smooth muscle cells (SMCs), and subjected to cyclic uniaxial strain. Mechanical strain enhanced NCSC proliferation and ERK2 phosphorylation. In addition, mechanical strain induced contractile marker calponin-1 within 2 days and slightly induced SM myosin within 5 days. On the other hand, mechanical strain suppressed the differentiation of NCSCs into Schwann cells. The induction of calponin-1 by mechanical strain was inhibited by neural induction medium but further enhanced by TGF-β. For NCSCs pre-treated with TGF-β, mechanical strain induced the gene expression of both calponin-1 and SM myosin. Our results demonstrated that mechanical strain regulates the differentiation of NCSCs in a manner dependent on biochemical factors and the differentiation stage of NCSCs. Understanding the mechanical regulation of NCSC differentiation will shed light on the development and remodeling of vascular tissues, and how transplanted NCSCs respond to mechanical factors.     

Effects of C-reactive protein on adipokines genes expression in 3T3-L1 adipocytes

Transplantation of skeletal myoblasts (SMs) has been investigated as a potential cardiac cell therapy approach. SM are available autologously, predetermined for muscular differentiation and resistant to ischemia. Major hurdles for their clinical application are limitations in purity and yield during cell isolation as well as the absence of gap junction expression after differentiation into myotubes. Furthermore, transplanted SMs do not functionally or electrically integrate with the host myocardium. Here, we describe an efficient method for isolating homogeneous SM populations from neonatal mice and demonstrate persistent gap junction expression in an engineered tissue. This method resulted in a yield of 1.4 × 10(8) high-purity SMs (>99% desmin positive) after 10 days in culture from 162.12 ± 11.85 mg muscle tissue. Serum starvation conditions efficiently induced differentiation into spontaneously contracting myotubes that coincided with loss of gap junction expression. For mechanical conditioning, cells were integrated into engineered tissue constructs. SMs within tissue constructs exhibited long term survival, ordered alignment, and a preserved ability to differentiate into contractile myotubes. When the tissue constructs were subjected to passive longitudinal tensile stress, the expression of gap junction and cell adherence proteins was maintained or increased throughout differentiation. Our studies demonstrate that mechanical loading of SMs may provide for improved electromechanical integration within the myocardium, which could lead to more therapeutic opportunities.     

Sorting of lipids and transmembrane peptides between detergent-soluble bilayers and detergent-resistant rafts

Specific proteins and lipids sequester to regions of cell membranes called rafts. Due to their high content of sphingomyelin (SM) and cholesterol, raft bilayers are thicker than nonraft bilayers and, at least at 4 degrees C, are resistant to Triton X-100 extraction. It has been postulated that rafts concentrate proteins with long transbilayer domains because of "hydrophobic matching" between the transbilayer domain and the thick bilayer hydrocarbon region. However, because the area compressibility and bending moduli of SM:cholesterol bilayers are larger than that of nonraft bilayers, there should be an energy cost to partition proteins or peptides into rafts. To determine the effects on peptide sorting of raft thickness and mechanical properties, we incorporated two transbilayer peptides (P-23, P-29) into bilayers composed of SM, dioleoylphosphatidylcholine, and cholesterol, separated detergent-soluble membranes (DSMs) from detergent-resistant membranes (DRMs), and measured their peptide and lipid compositions. P-23 and P-29 were designed to have transbilayer domains that matched the hydrocarbon thicknesses of DSMs and DRMs, respectively. At both 4 degrees C and 37 degrees C DSMs were enriched in dioleoylphosphatidylcholine and DRMs were enriched in SM and cholesterol. At both temperatures both P-23 and P-29 preferentially localized to DSMs, demonstrating the importance of bilayer mechanical properties relative to hydrophobic mismatch. However, at 37 degrees C significantly more P-29 than P-23 was located in DRMs, implying that hydrophobic matching played a role in peptide sorting at physiological temperature. These experiments demonstrate that the sorting of peptides as measured by detergent extraction is temperature-dependent and both bilayer mechanical properties and hydrophobic matching impact peptide distribution between DSMs and DRMs.     

Salvia miltiorrhiza attenuates the changes in contraction and intracellular calcium induced by anoxia and reoxygenation in rat cardiomyocytes

The aim of the present study is to investigate the effect of Salvia miltiorrhiza (SM) on contraction and the intracellular calcium of isolated ventricular myocytes during normoxia or anoxia and reoxygenation using a video tracking system and spectrofluorometry. Cardiac ventricular myocytes were isolated enzymatically by collagenase and exposed to 5 min of anoxia followed by 10 min of reoxygenation. SM (1-9 g/L) depressed both contraction and the [Ca(2+)](i) transient in a dose-dependent manner. SM did not affect the diastolic calcium level and the sarcolemmal Ca(2+) channel of myocytes but decreased the caffeine-induced calcium release. During anoxia, the +/-dL/dtmax, amplitudes of contraction (dL) of cell contraction and [Ca(2+)](i) transients were decreased, while the diastolic calcium level was increased. None of the parameters returned to the pre-anoxia level during reoxygenaton. However, SM (3 g/L) did attenuate the changes in cell contraction and intracellular calcium induced by anoxia and reoxygenation. It is concluded that SM has different effects on normoxic and anoxic cardiomyocytes. The SM-induced reduction of changes in contraction and intracellular calcium induced by anoxia/reoxygenation indicates that SM may be beneficial for cardiac tissue in recovery of mechanical function and intracellular calcium homeostasis.     

Osteoporosis As The Sole Manifestation of Systemic Mastocytosis In A Young Man

ObjectiveTo highlight the difficulty involved in mak ing a diagnosis of systemic mastocytosis (SM) when it manifests solely as osteoporosis.MethodsWe present a detailed case report and review the literature regarding the work-up of secondary osteopo rosis and the diagnosis and treatment of SM. Other cases of SM presenting as osteoporosis in male patients are also described.ResultsA 35-year-old man presented with back pain after weight lifting and was diagnosed with a T7 vertebral compression fracture. A dual-energy x-ray absorptiom etry scan resulted in a T-score of − 3.2 in the spine and of − 1.9 and − 2.4 in the hip and femoral neck areas, respec tively. Results of standard tests for secondary osteoporo sis including calcium, phosphorus, 25-hydroxyvitamin D, kidney and liver function, thyroid function, testosterone level, and midnight salivary cortisol were normal. Further testing revealed a high serum tryptase level of 26.8 μg/L (reference range, < 11.4) and elevated urinary histamine at 39.1 μg/g creatinine (reference range, < 35). Bone marrow biopsy confirmed the diagnosis of mastocytosis.ConclusionThe rare diagnosis of SM is diffi cult when there is little clinical suspicion and remains a challenge to endocrinologists and other physicians. The condition should be suspected in young male patients with no other obvious cause of osteoporosis. (Endocr Pract. 2012; 18:e158 e161)     

The role of intra-abdominal pressure in spinal unloading

Previous studies on how an increase in intra-abdominal pressure (IAP) effects the loading of the lumbar spine during back extension show diverging results. From a critical review of the literature we deduce a simplified, but consistent, model of the mechanisms involved in IAP-induced unloading of the lumbar spine. The model is then expanded by explicitly incorporating equilibrium equations for the pressurised abdomen and the abdominal wall. It is shown that the unloading effect of IAP can be viewed as that of a pressurised column of fixed cross-sectional area, between the rib cage and pelvis. Different abdominal forms are examined and a form with zero longitudinal curvature is found to have some important mechanical benefits for the generation of IAP-induced alleviation of compressive loading of the lumbar spine.     

Effects of disc degeneration on neurophysiological responses during dorsoventral mechanical excitation of the ovine lumbar spine

Mechanisms of spinal manipulation and mobilization include the elicitation of neuromuscular responses, but it is not clear how these responses are affected or altered by disc degeneration. We studied the neurophysiological responses of the normal and degenerated ovine spine subjected to mechanical excitation (varying force amplitude and duration) consistent with spinal manipulative therapy (SMT). Needle electromyographic (EMG) multifidus muscle activation adjacent to the L3 and L4 spinous processes and compound action potentials (CAPs) of the L4 nerve roots were measured during the application of dorsoventral mechanical excitation forces designed to mimic SMT force–time profiles used routinely in clinical practice. The magnitude and percentage of positive EMG responses increased with increasing SMT force magnitude, but not SMT pulse duration, whereas CAP responses were greatest for shorter duration pulses. Disc degeneration was associated with a reduction (20–25%) in positive EMG responses, and a concomitant increase (4.5–10.2%) in CAP responses.     

Risk Factors and Outcomes of Stenotrophomonas maltophilia Bacteraemia: A Comparison with Bacteraemia Caused by Pseudomonas aeruginosa and Acinetobacter Species

Stenotrophomonas maltophilia (SM) is an important nosocomial pathogen that exhibits intrinsic resistance to various antimicrobial agents. However, the risk factors for SM bacteraemia have not been sufficiently evaluated. From January 2005 to September 2012, we retrospectively compared the clinical backgrounds and outcomes of SM bacteraemic patients (SM group) with those of bacteraemic patients due to Pseudomonas aeruginosa (PA group) or Acinetobacter species (AC group). DNA genotyping of the SM isolates using the Diversilab system was performed to investigate the genetic relationships among the isolates. The SM, PA, and AC groups included 54, 167, and 69 patients, respectively. Nine of 17 patients in the SM group receiving trimethoprim-sulfamethoxazole prophylaxis developed SM bacteraemia. Independent risk factors for SM bacteraemia were the use of carbapenems and antipseudomonal cephalosporins and SM isolation within 30 days prior to the onset of bacteraemia. Earlier SM isolation was observed in 32 of 48 patients (66.7%) with SM bacteraemia who underwent clinical microbiological examinations. Of these 32 patients, 15 patients (46.9%) had the same focus of bacteraemia as was found in the previous isolation site. The 30-day all-cause mortality rate among the SM group (33.3%) was higher than that of the PA group (21.5%, p = 0.080) and the AC group (17.3%, p = 0.041). The independent factor that was associated with 30-day mortality was the SOFA score. DNA genotyping of SM isolates and epidemiological data suggested that no outbreak had occurred. SM bacteraemia was associated with high mortality and should be considered in patients with recent use of broad-spectrum antibiotics or in patients with recent isolation of the organism.