Diaphragm pacing in spinal cord injury can significantly decrease mechanical ventilation in multicenter prospective evaluation.

BACKGROUND: Cervical spinal cord injury (SCI) can lead to dependence on mechanical ventilation (MV) with significant morbidity and mortality. The diaphragm pacing system (DPS) was developed as an alternative to MV. METHODS: We conducted a prospective single-arm study of DPS in MV-dependent patients with high SCI and intact phrenic nerves. Following device acclimation, pacing effectiveness to provide ventilation was evaluated. The primary endpoint was the number who could use DPS to breathe for 4 continuous hours without MV. Secondary endpoints included the number of patients that could use DPS 24 h/day free of MV and the ability of DPS to maintain clinically acceptable tidal volume (Vt). In addition, we conducted a meta-analysis that included the prospective study along with data from four recently published studies to evaluate DPS hourly use. RESULTS: Fifty-three patients were implanted in the prospective study. Most were male (77.4%) with a median time from injury to treatment of 28.3 (IQR: 12.1, 83.3) months. Four- and 24-h use occurred in 96.2% (95% CI: 87.0%, 99.5%) and 58.5% (95% CI: 44.1%, 74.9%), respectively. Four and 24-h results in the meta-analysis cohort (n = 196) exhibited similar results 92.2% (95% CI: 82.6%, 96.7%) and 52.7% (95% CI: 36.2%, 68.6%) using DPS for 4 and 24 h, respectively. DPS use significantly exceeded the calculated basal tidal volume requirements by a mean of 48.4% (95% CI: 37.0, 59.9%; p < 0.001). CONCLUSIONS: This study demonstrates that in most ventilator-dependent patients, diaphragm pacing can effectively supplement or completely replace the need for MV and support basal metabolic requirements.

Epidemiology of spinal fractures and associated spinal cord injuries in Iceland.

STUDY DESIGN: A retrospective epidemiological study. SETTING: Landspítali University Hospital, Iceland. OBJECTIVES: Assessment of epidemiological data and risk factors for traumatic spinal fractures (SFs) and associated spinal cord injury (SCI). METHODS: A retrospective review of hospital admissions due to traumatic SFs during a 5-year period, with analysis of epidemiological parameters and occurrence of concomitant SCI. Patients with asymptomatic SFs and non-traumatic SCI were excluded. RESULTS: A total of 487 patients were diagnosed with a SF or 310 PMI (per million inhabitants), 42 of them (9%, 27 PMI) with an associated SCI. The mean age was 56 years, males were 57%. Falls were the leading cause of both SFs (49%) and SCIs (43%). Low falls (<1 m) caused SFs more often in elderly women (67%, mean age 77 years) and more than 96% were without SCI. Road traffic accidents (RTA) caused 31% of SFs and 26% of SCIs. Seat belts were not used in 20% of car accidents, but information was missing in 27%. Sports/leisure-related accidents caused SFs in 12% of cases, whereof horseback riding accidents were the most common (36%). CONCLUSIONS: SFs led to SCI in 9% of patients. Several risk factors were common for SFs and SCIs but two major differences were seen: SFs without SCI were most common in older women due to low falls, while the risk of a concomitant SCI increased in young patients, in males, in falls from high levels and when driving without using seat belts. Preventive efforts should therefore be directed towards these risk factors.

Applications of inflammation-derived gingival stem cells for testing the biocompatibility of dental restorative biomaterials.

BACKGROUND: Normal or inflamed gingival tissues are regarded as a source of mesenchymal stem cells (MSCs) abundant and easily accessible through minimally invasive dental procedures. Due to the proximity of dental resin composites to gingival tissues and to the possible local cytotoxic effect of the eluted components, gingiva-derived MSCs could be used to investigate the biocompatibility of dental biomaterials. PURPOSE: The present research aimed to isolate (MSCs) from inflamed and normal gingiva, to fully characterize them and to observe their behavior in relation with some commercial resin composite materials and one experimental material. MATERIAL AND METHODS: Following their isolation, putative MSCs from both gingival sources were grown under the same culture conditions and characterized by immunophenotyping of cell surface antigens by flow-cytometry and transcription factors by immunocytochemical staining. Moreover, stemness gene expression was evaluated by RT-PCR analysis. Multipotent mesenchymal differentiation potential was investigated. Osteogenic and neurogenic differentiated cells were highlighted by immunocytochemical staining, chondrogenic cells by cytochemical staining, and adipocytes by cytochemical staining and spectrophotometry, respectively. Resin composite cytotoxicity was evaluated by cell membrane fluorescent labeling with PKH 26 and MTT assay. The results of PKH labeling were statistically analysed using two-way RM ANOVA with Bonferroni post-tests. For MTT assay, two-way RM ANOVA with Bonferroni post-tests and unpaired t test with Welch's correction were used. RESULTS: A similar expression pattern of surface markers was observed. The cells were positive for CD105, CD73, CD90, CD49e, CD29, CD44 and CD166 and negative for CD45, CD34, CD14, CD79, HLA-DR and CD117 indicating a mesenchymal stem cell phenotype. The qRT-PCR analysis revealed a low gene expression for NOG, BMP4 and Oct3/4 and an increased expression for Nanog in both cells lines. Immunocytochemical analysis highlighted a more intense protein expression for Nanog, Oct3/4 and Sox-2 in MSCs derived from normal gingiva than from inflamed gingiva. Multipotent differentiation capacity of MSCs isolated from both sources was highlighted. The tested materials had no hazardous effect on MSCs as the two cell lines developed well onto resin composite substrates. Cell counting revealed some significant differences in the number of PKH-labeled MSCs at some experimental moments. Also, some differences in cell viability were recorded indicating better developmental conditions offered by some of the tested biomaterials. CONCLUSIONS: The experimental resin composite behaved like the most biocompatible commercial material. Inflamed gingiva-derived MSCs retain their stem cell properties and could be used as a valuable cell line for testing dental biomaterials.

[Epidemiology of Spinal Cord Injury in Iceland from 1975 to 2014].

INTRODUCTION: Traumatic spinal cord injury (TSCI) is serious and often has long-term consequences. Since no cure has been found the emphasis has been on preventive measures. The incidence of TSCI varies between countries and the epidemiology has been changing. The aim of this study was to gather epidemiological data on patients with TSCI in Iceland and search for risk factors. MATERIAL AND METHODS: Hospital records of everyone diagnosed with TSCI in 1975-2014 admitted to Landspitali University Hospital were reviewed and information gathered on incidence, age, gender and causes of injury. The American Spinal Injury Association Impairment Scale (AIS) was used to assess the extent of TSCI. RESULTS: A total of 233 patients were diagnosed with TSCI during the study period or 26 per million annually on average. Males were 73% and the mean age was 39 years. Traffic accidents were the most common cause of TSCI. The majority were car rollovers in rural areas. Around 50% did not use a seatbelt. The second most common cause of TSCI were falls. The most common sport/leisure accidents were those related to horseback-riding and winter sports. A third of patients had a complete SCI. At discharge 9% had gained full recovery. CONCLUSIONS: Safe roads and good traffic culture are essential factors in the prevention of serious traffic accidents. Strict safety regulations in the work place and an investigation of causes of falls amongst the elderly could decrease SCIs due to falls. Further preventive measures and protective equipment could possibly be of use in sport- or leisure-related activities. Key words: Traumatic spinal cord injury, incidence, age, gender, causes, extent. Correspondence: Pall E. Ingvarsson, palling@landspitali.is.

Equine Embryo Sexing and Ultrasonographic Foetal Sexing - Interests and Applicability.

The ability to choose the sex of the offspring is of upmost economic importance for horse breeders. Unlike other species, horses present several reproductive peculiarities that interfere with assisted reproductive technologies used in other large animals (such as bovine) and make them difficult to apply. Thus, there is a great interest to determine the sex of the offspring as soon as possible. This has led to the development of several technologies to serve this purpose, which can be classified into two categories. One is equine embryo sexing by either non-invasive biotechnological methods, such as monitoring of X-linked enzymes before X chromosome inactivation and detection of sex-specific antigen, or by invasive biotechnological methods, such as cytogenetic analysis and polymerase chain reaction (PCR). The other one is equine foetus sexing using ultrasound scanning in different stages of its development (early, mid or late), by different approaches (transrectally or transabdominally). This can be performed with classic B-mode ultrasound machines or using 3D-mode and Doppler-mode scanners. This review article offers a comprehensive overview of the current status of these procedures as well as an assessment of their interests and applicability.

Evaluation of bovine embryo biopsy techniques according to their ability to preserve embryo viability.

The purpose of this research was to evaluate three embryo biopsy techniques used for preimplantation genetic diagnosis (PGD) in cattle and to recommend the least invasive one for current use, especially when PGD is followed by embryo cryopreservation. Three hundred bovine embryos were biopsied by either one of the needle, aspiration or microblade method, and then checked for viability by freezing/thawing and transplantation to recipient cows. The number of pregnancies obtained after the transfer of biopsied frozen/thawed embryos was assessed 30 days later using ultrasounds. The results were significantly different between the three biopsy methods: the pregnancy rate was of 57% in cows that received embryos biopsied by needle, 43% in cows that received embryos biopsied by aspiration, and 31% in cows that received embryos biopsied by microblade. Choosing an adequate biopsy method is therefore of great importance in embryos that will undergo subsequent cryopreservation, as it significantly influences their viability after thawing.

Mesenchymal stem cell irradiation in culture engages differential effect of hyper-fractionated radiotherapy for head and neck cancers.

PURPOSE: The purpose of this study was to challenge current knowledge on the potential therapeutic advantages of stem cells in radiotherapy by developing an in vitro model of the healthy tissue surrounding or replacing the widely resected tumor. After radical surgery, the start of radiotherapy is often delayed due to wound healing process, with potential loss of the opportunity for treating microscopic disease instead of macroscopic early recurrence. Hyperfractionated radiotherapy, contrary to the standard one, can extend the limits of radical surgery and shorten the gap before the onset of postoperative radiotherapy, with potential improvement in local control. METHODS: By using both mesenchymal stem cells and pre-differentiated osteoblasts, cultured in proper pro-osteogenic media after cell irradiation, we investigated both the differences in the response to DNA damage between lineages undergoing differentiation in culture and the intensity of the mineralization process. RESULTS: Ionizing radiation stimulated stem cell proliferation and differentiation at 0.5 Gy and 1 Gy, thus confirming in vitro the clinical results of hyperfractionated irradiation randomized trials in head and neck cancers -HNCs-. CONCLUSION: To our knowledge, this study is the first to investigate the biophysics of low dose gamma irradiation on stem cell culture, focusing on the potential applications in radiation oncology. For advanced oral cavity and oropharyngeal cancers, as radical surgery often implies major bone resection, the use of mesenchymal stem cells as bone reconstruction vectors might shorten the onset of adjuvant hyperfractionated radiotherapy which enhances the mineralization process. As postoperative radiotherapy has recently being revisited for osteosarcoma, this scenario could impact also on bone reconstruction process in this pathology.

Complete worldwide operative experience in laparoscopic diaphragm pacing: results and differences in spinal cord injured patients and amyotrophic lateral sclerosis patients.

BACKGROUND: Diaphragm movement is essential for adequate ventilation, and when the diaphragm is adversely affected patients face lifelong positive-pressure mechanical ventilation or death. This report summarizes the complete worldwide multicenter experience with diaphragm pacing stimulation (DPS) to maintain and provide diaphragm function in ventilator-dependent spinal cord injury (SCI) patients and respiratory-compromised patients with amyotrophic lateral sclerosis (ALS). It will highlight the surgical experiences and the differences in diaphragm function in these two groups of patients. METHODS: In prospective Food and Drug Administration (FDA) trials, patients underwent laparoscopic diaphragm motor point mapping with intramuscular electrode implantation. Stimulation of the electrodes ensued to condition and strengthen the diaphragm. RESULTS: From March of 2000 to September of 2007, a total of 88 patients (50 SCI and 38 ALS) were implanted with DPS at five sites. Patient age ranged from 18 to 74 years. Time from SCI to implantation ranged from 3 months to 27 years. In 87 patients the diaphragm motor point was mapped with successful implantation of electrodes with the only failure the second SCI patient who had a false-positive phrenic nerve study. Patients with ALS had much weaker diaphragms identified surgically, requiring trains of stimulation during mapping to identify the motor point at times. There was no perioperative mortality even in ALS patients with forced vital capacity (FVC) below 50% predicted. There was no cardiac involvement from diaphragm pacing even when analyzed in ten patients who had pre-existing cardiac pacemakers. No infections occurred even with simultaneous gastrostomy tube placements for ALS patients. In the SCI patients 96% were able to use DPS to provide ventilation replacing their mechanical ventilators and in the ALS studies patients have been able to delay the need for mechanical ventilation up to 24 months. CONCLUSION: This multicenter experience has shown that laparoscopic diaphragm motor point mapping, electrode implantation, and pacing can be safely performed both in SCI and in ALS. In SCI patients it allows freedom from ventilator and in ALS patients it delays the need for ventilators, increasing survival.

Manual transport in Parkinson's disease.

We analyze hand dexterity in Parkinson's disease patients (PD) and control subjects using a natural manual transport task (moving an object from one place to another). Eight PD patients and 10 control subjects carried out the task repeatedly at maximum speed both in off and on medicated status. The movement parameters and the grip and load forces were recorded. Using the force and velocity signals, 10 subsequent phases of the transport movement were defined and their durations were measured. The difference between the control group and the test group in off and on was established statistically using non-parametric methods. There was slowed reaching and a striking disturbance of establishing the precision grip in PD. The transport capabilities were impaired differentially. Although acceleration and reaching sufficient height of the lift were disturbed in PD subjects, transport of the object toward the target position was almost normal. A partial disturbance was observed when cancelling the grip. Dopaminergic medication improved only specific hand skills, especially establishment of the precision grip and one of the four transport phases. A long movement path was more sensitive for movement disturbance in Parkinson's disease than a short one.

Grip and load force coordination during a manual transport movement: findings in healthy participants.

During transport of an object using the precision grip with thumb and index finger, a modulation of the grip force is needed in response to the forces evoked by the movement. We measured the grip force (GF) and the load force (LF) in 10 healthy participants moving a 640-g object forward and upward. The task was repeated with various speeds. There were considerable changes with speed of the LF trajectory but not of the GF trajectory. A loss of synergy between GF and LF appeared in fast lifts. This is in contrast to the close coupling between load force and grip force repeatedly demonstrated during simple lifts. We suggest that (a) speed should be considered as an input parameter for movement planning, and (b) regulation of GF and of LF are independent under certain conditions. We discuss whether the grip-load force synergy should be considered a special case rather than a more general principle

Differential heparin inhibition of skeletal muscle alpha-dystroglycan binding to laminins.

The laminin binding properties of alpha-dystroglycan purified from rabbit skeletal muscle membranes were examined. In a solid phase microtiter assay, 125I-laminin (laminin-1) bound to purified alpha-dystroglycan in a specific and saturable manner with a half-maximal concentration of 8 nM. The binding of 125I- alpha-dystroglycan to native laminin and merosin (a mixture of laminin-2 and -4) was also compared using the solid phase assay. The absolute binding of 125I- alpha-dystroglycan to laminin (6955 +/- 250 cpm/well) was similar to that measured for merosin (7440 +/- 970 cpm/well). However, inclusion of 1 mg/ml heparin in the incubation medium inhibited 125I-alpha-dystroglycan binding to laminin by 84 +/- 4.3% but inhibited 125I-alpha-dystroglycan binding to merosin by only 17 +/- 5.2%. Similar results were obtained with heparan sulfate, while de-N-sulfated heparin, hyaluronic acid, and chondroitin sulfate had no differential effect. These results were confirmed by iodinated laminin and merosin overlay of electrophoretically separated and blotted dystrophin-glycoprotein complex. In contrast to the results obtained with skeletal muscle alpha-dystroglycan, both laminin and merosin binding to purified brain alpha-dystroglycan was significantly inhibited by heparin. Our data support the possibility that one or more heparan sulfate proteoglycans may specifically modulate the interaction of alpha-dystroglycan with different extracellular matrix proteins in skeletal muscle.

[Study of the ocular toxicity of ethambutol]. / Studiu privind toxicitatea oculara a etambutolului.

Thirty cases were studied, of children aged between 4 and 5 years, with latent or manifest (overt) pulmonary tuberculosis under treatment with etambutol (EMB) administered intermittently (2/7) in amounts of 25 mg. per kg of body weight. Ophtalmological investigations consisted in evaluation of the visual acuity, of the visual field, of the chromatic sense, pupillary reflexes and an examination of the fundus. These were performed before the start of the treatment, then at 3 and 6 months after the treatment was begun. No cases of toxic ocular manifestations was recorded. The results are discussed on the basis of data from the literature, and care is recommended in the administration of etambutol.

[Fatalities in a rehabilitation center for cardiovascular diseases (author's transl)]. / Todesfälle an einer Rehabilitationsklinik für Herz- und Kreislaufkrankheiten

From 1967 until the end of 1974, a total of 32 524 treatments were carried out at the Höhenried clinic. There were 40 fatal incidents, corresponding to a mortality rate of 0.12%. 5386 treatments were carried out in 3606 infarction patients. Of these, 29 patients died, which, related to the treatments, corresponds to a mortality rate of 0.53% and, related to the number of infarction patients, to 0.80%. The main cause of death was acute cardiac death. 10 fatal incidents occurred in temporal relation to kinesitherapy. Retrospectively, severe ECG changes due to infarction, pathological reactions to stress as well as disorders of cardiac rhythm and cardiac hypertrophy can be regarded as being indicative of a particular danger to patients.