Retrospective analysis of local injection site adverse reactions associated with 230 allogenic administrations of bone marrow-derived mesenchymal stem cells in 164 horses.

BACKGROUND: Bone marrow-derived mesenchymal stem cells (BM-MSCs) are frequently used in the treatment of musculoskeletal injuries. Fully characterised cells that are readily available for use is optimum. Allogenic BM-MSCs can satisfy the need for rapid treatment, however, their safety has been questioned. OBJECTIVES: Objectives were to characterise BM-MSCs from an adult donor horse, in vitro, and to identify and describe adverse reactions that occurred following their injection into other horses. We hypothesised that BM-MSCs capable of proliferation, differentiation and lacking MHC II from one donor could be implanted into another individual without significant adverse reactions and the frequency of adverse reactions in clinical cases would be similar to that previously reported for autologous BM-MSCs. STUDY DESIGN: Retrospective clinical study. METHODS: BM-MSCs were proliferated and characterised from one donor and cryopreserved for clinical use. Medical records for horses injected with allogenic BM-MSCs from this donor at a single hospital were used. After routine lameness exam, lesions were identified using diagnostic ultrasound or MRI. Post injection reaction was defined as increased pain, swelling, or heat at or near injection site, or increased lameness. Treatments required for each reaction were noted. RESULTS: BM-MSCs proliferated and underwent differentiation. Cells were found to be negative for MHC-II (<2%) and were viable after cryopreservation and shipping. Ten of 230 (4.35%) injections were noted to be associated with an adverse reaction. Adverse reactions occurred in synovial structures (n = 3) and in soft tissues (n = 7). MAIN LIMITATIONS: This investigation could underestimate the number and severity of reactions. Mild reactions, such as synovitis, may have been missed. Also, anti-inflammatory drugs could overshadow mild reactions, making them less likely to be detected. CONCLUSIONS: Fully characterised allogenic BM-MSCs originating from a single donor horse can be administered to horses with soft tissue injuries with a low rate of adverse reaction. The Summary is available in Portuguese - see Supporting Information.

Mind the gap: can videolaryngoscopy bridge the competency gap in neonatal endotracheal intubation among pediatric trainees? a randomized controlled study.

BACKGROUND: To study the impact of videolaryngoscopy (VL) on intubation success among pediatric trainees compared with direct laryngoscopy (DL). METHODS: One hundred pediatric residents were enrolled in a randomized, crossover, simulation study comparing VL to DL. Following a didactic session on neonatal intubation, residents intubated a standard neonatal mannequin. Three Neonatal Resuscitation Program (NRP) scenarios were then conducted, followed by a mannequin intubation with the alternate device. Number of attempts and time to intubation were recorded for all intubations. RESULTS: Proportion of successful intubations on first attempt was greater with VL compared with DL (88% versus 63%; P=0.008). The DL group increased success after crossover with VL (63% versus 89%; P=0.008). Exposure to VL also reduced intubation time after device crossover (median intubation time: 31 versus 17 s; P=0.048). CONCLUSIONS: VL increased the success of endotracheal intubation by pediatric residents in simulation, with skills transferrable to DL.

In vitro analysis of equine, bone marrow-derived mesenchymal stem cells demonstrates differences within age- and gender-matched horses.

REASONS FOR PERFORMING THE STUDY: Stem cell therapies are used routinely in equine practice. Most published reports characterise stem cells derived from younger horses; however, middle-aged horses are often in athletic performance, and experience degenerative medical conditions. Thus, mesenchymal stem cells (MSCs) from this group should be investigated. OBJECTIVE: To describe differences in in vitro adherence, proliferation and potential for differentiation of equine bone marrow-derived MSCs (equine BMMSCs) harvested from middle-aged (10-13 years old) female donors. STUDY DESIGN: Descriptive study of stem cell characteristics. METHODS: Equine BMMSCs from 6 horses were cultured in vitro and evaluated for viability, proliferation, osteogenesis, chondrogenesis, adipogenesis, cluster-of-differentiation markers and gene expression. RESULTS: Equine BMMSCs from all 6 donors demonstrated fibroblastic, cellular morphology, adherence to plastic and expression of cluster-of-differentiation markers. They varied in their rate of proliferation and trilineage differentiation. The equine BMMSCs of one of 6 donors demonstrated a higher rate of proliferation, enhanced ability for cell passaging and a more robust in vitro differentiation. Comparatively, equine BMMSCs from 2 donors demonstrated a lower rate of proliferation and lack of osteogenic and chondrogenic differentiation. CONCLUSION: The results of this study confirm that donor-to-donor variation in equine BMMSCs exists and this variation can be documented using in vitro assays. Subjective assessment suggests that the rate of proliferation tends to correlate with differentiation potential.

Impact of an outbreak of severe acute respiratory syndrome on a hospital in Taiwan, ROC.

STUDY OBJECTIVE: To estimate the impact of the severe acute respiratory syndrome (SARS) outbreak in early 2003 on a tertiary care hospital in Taiwan, ROC. METHODS: The study estimated the utilisation of resources related to infection control, SARS related medical services, and routine medical services, and SARS related medical outcomes at National Cheng Kung University Hospital (NCKUH) from 25 March to 16 June 2003 through a cross sectional survey of hospital records. RESULTS: A mean of 5100 persons per day (95%CI 4580 to 5610) underwent fever screening at the outpatient and emergency department (ED) entrances to the hospital, of which 35 per day (95% CI 30 to 40) were referred for further evaluation for suspected or probable SARS. ED isolation surge capacity was created via 12 new beds outside the ED: eight for SARS assessment, three for patients awaiting in hospital bed assignment, and one for resuscitation. A total of 382 patients were fully evaluated for suspected or probable SARS outside the ED, of which 27 were admitted. The mean numbers of outpatient clinic patient visits, ED visits, ED trauma patient visits, ED admissions, hospital admissions, and operative procedures decreased during the outbreak. Thirty eight patients were hospitalised with suspected SARS, of which three received the final diagnosis of probable SARS. Two patients with probable SARS died. No cases of nosocomial SARS transmission occurred. CONCLUSIONS: This SARS outbreak was associated with substantial use of hospital and ED resources aimed at infection control, comparatively less use of resources related to the medical care of patients with suspected or probable SARS, and decreased use of routine medical services.

Emergency medicine in Southern Brazil.

Emergency medicine is developing rapidly in southern Brazil, where elements of both the Franco-German and the Anglo-American models of emergency care are in place, creating a uniquely Brazilian approach to emergency care. Although emergency medical services (EMS) in Brazil have been directly influenced by the French mobile EMS (SAMU) system, with physicians dispatched by ambulances to the scenes of medical emergencies, the first American-style emergency medicine residency training program in Brazil was recently established at the Hospital de Pronto Socorro (HPS) in Porto Alegre. Emergency trauma care appears to be particularly developed in southern Brazil, where advanced trauma life support is widely taught and SAMU delivers sophisticated trauma care en route to trauma centers designated by the state.

A survey of emergency medicine in 36 countries.

OBJECTIVE: To assess the current level of development of emergency medicine (EM) systems in the world. DESIGN: Survey of EM professionals from 36 countries during a 90-day period from Aug. 25 to Nov. 24, 1998. PARTICIPANTS: Thirty-six EM professionals from 36 countries and 6 continents completed the survey. Thirty-five (97%) were physicians, of whom 25 (69%) gave presentations at 1 of 4 international EM conferences during the study period. Three potential participants from 3 countries were excluded because of language barriers. Five additional participants from 5 other countries did not respond within the study period and were excluded. MEASUREMENTS: Respondents completed a 103-question questionnaire about the presence of EM specialty, academic, patient care, information and management systems and the factors influencing the future of EM in their countries. RESULTS: The overall response rate was 88%. Nearly all respondents (97%) stated that their countries had hospital-based emergency departments (EDs). More than 80% of respondents reported that their countries have emergency medical services (EMS), national EMS activation phone numbers and ED systems for pediatric emergency care. More than 70% stated that their countries had national EM organizations, EM research, ED systems for patient transfer and peer review and emergency physician (EP) training in Advanced Cardiac Life Support (ACLS) and the ability to perform rapid sequence intubation. More than 60% reported ED systems for trauma care and triage and EP training in Advanced Trauma Life Support (ATLS) and the ability to perform thrombolysis for acute myocardial infarction. Fifty percent reported EM residency training programs, official recognition of EM as an independent specialty, and EM journals. CONCLUSIONS: Basic emergency medicine components now exist in the majority of countries surveyed. These include many specialty, academic, patient care and administrative systems. The foundation for further EM development is widely established throughout the world.

International emergency medicine and the recent development of emergency medicine worldwide.

Emergency medicine is being established as a unique and independent specialty throughout the world. Two major models of emergency care delivery exist in the world today: the Anglo-American and the Franco-German model. Most countries developing new systems of emergency care are following the Anglo-American model and are recapitulating the sequence of steps taken to establish the systems of emergency medicine in the United States. The most important step in the development of emergency medicine in other countries is the recognition that emergency medicine incorporates a unique body of knowledge requiring specialized practitioners or emergency physicians. A global network of international emergency medicine is assisting the development of emergency medicine worldwide and now includes international organizations, academic institutions, and individuals in countries where emergency medicine is mature and their counterparts in countries where emergency medicine is developing. The multilevel exchange of information through various modalities, such as international conferences, physician exchange programs, and print or electronic media, is playing a vital role in the search for internationally applicable systems of emergency care.

The recent development of emergency medicine in South Korea.

Emergency medicine has developed rapidly in South Korea in the past decade, giving Korea one of the most advanced systems of emergency medical care in Asia. This article reviews the overall health care system and medical climate in Korea, as well as the great progress made in establishing emergency medicine as a specialty. It also describes the many improvements implemented in academic emergency medicine, emergency patient care, and emergency medicine management systems. Although the current economic crisis offers new challenges, much optimism remains about the future of this new Korean specialty.

Colorectal neoplasms detected colonoscopically in at-risk members of colorectal cancer families stratified by the demonstration of DNA microsatellite instability.

This study compared colonoscopic findings in families meeting the Amsterdam criteria (A) for hereditary non-polyposis colorectal cancer (HNPCC) but stratified according to whether the familial cancers showed DNA microsatellite instability. DNA was extracted from paired samples of normal and cancer, and microsatellite instability was analysed at up to six loci. Families were termed replication error positive (RER+) when at least 50% of tumours tested per family were positive. Of 26 families studied 17 were RER+ and 9 were RER-. Cancers in the A/RER- families showed no right-sided predilection (P < 0.001). Colonoscopies have been performed on 182 at-risk members of A/RER+ families and 60 members of A/RER- families. More of the at-risk members of A/RER-families were found to have adenomas at colonoscopy (P = 0.095), but these were smaller than those of A/RER+ families (P = 0.19). The adenoma:carcinoma ratio was twice as high in A/RER- families (13:1) as in A/RER+ families (7:1). One of the A/RER- families had hyperplastic polyposis. The others do not appear to have attenuated familial adenomatous polyposis and are similar to the adenoma families or late-onset colorectal cancer families described by others. This study illustrates the importance of molecular technology in separating HNPCC from syndromes with overlapping phenotypes.

Changing Children's Perceptions of the Elderly:.

Age-integrated programming has become an effective way to bring the young and old closer together. This article reviews some of the relevant literature and then describes a study involving the Intergenerational Partners Project, a program which stressed the use of age-integrated friendship. The project involved a number of activities shared by fourth graders and elderly volunteers. The Children's Perception of Aging and Elderly (CPAE) inventory administered before and after the program indicated significant attitude improvement toward the elderly by participating students. Other information from the youth and elderly participants also indicated positive qualities of the partners program. The format used to organize the project is presented and the planned activities are identified. Recommendations for intergenerational programming are discussed.

Erythropoietin levels with treatment of obstructive sleep apnea.

The effect of nasal continuous positive pressure (CPAP) treatment on erythropoietin (EPO) was examined by measuring diurnal serum EPO levels before and twice (over the 3rd day and over 1 day on recall after > or = 1 mo of therapy) after initiation of treatment in 12 obstructive sleep apnea syndrome patients with normal hemoglobin, hematocrit, creatinine, blood urea nitrogen, and albumin levels. Over each study day, oxygen saturation was measured by an ambulatory pulse oximetry system. Patients spent 27 +/- 9% (SE) of time below oxygen saturation of 88% vs. 2.1 +/- 0.6% after initiation of nasal CPAP treatment (P < 0.01). The number of desaturation events per hour of sleep before nasal CPAP treatment was 62 +/- 6 vs. 9 +/- 2 with nasal CPAP (P < 0.01). EPO levels measured by radioimmunoassay were drawn every hour before and at 3 days (n = 9) and before and at recall (n = 0) after initiation of CPAP therapy. The mean serum EPO level was higher before treatment (61 +/- 14 mU/ml) than that at 3 days (38 +/- 10 mU/ml, P < 0.01) or at recall (32 +/- 7 mU/ml, P < 0.01). We conclude that nasal CPAP treatment of sleep-disordered breathing will reduce diurnal levels of EPO.

Nasal response to carrot and lettuce challenge in allergic patients.

BACKGROUND: Food allergies are usually recognized by historical triggers; yet, on occasion, objective testing may be needed to demonstrate allergic causes more convincingly. OBJECTIVE: Two atopic adult patients presented with respiratory and/or ocular symptoms with an unusual association to handling or eating of vegetables. A third atopic patient presented without attribution of symptoms to vegetable exposure. In all, work-up had revealed positive skin tests and in vitro assays for specific IgE to carrot and/or lettuce; none had gastrointestinal complaints. METHODS: To assess further these unusual histories and/or IgE antibody findings, laboratory challenge was performed with nasal resistance being used as a monitor of rhinitic reaction. RESULTS: The first two patients had prolonged nasal objective responses to challenge; the third had a transient response to one of two challenges. CONCLUSION: We conclude that lettuce and carrot can account for clinically significant IgE-mediated allergic reactions, manifested by nasal obstruction. This laboratory reaction to foodstuffs appears to correlate with patient-reported upper airway and ocular symptoms.

Functional electrical stimulation and respiration during sleep.

During obstructive sleep apnea (OSA), respiratory activation of upper airway muscles, particularly genioglossus, is ineffective during sleep. Functional electrical stimulation (FES) of muscles reportedly reduces the number and length of OSAs. Our goals were to examine the effect of FES on sensation during wakefulness and on OSA events. Studies were performed in 11 subjects: 4 healthy asymptomatic subjects and 7 patients with OSA. Surface electrodes placed on the submental region produced discomfort; however, during sleep, the stimulus intensity producing arousal was significantly greater than that producing barely tolerable discomfort during wakefulness. Additionally, we developed a protocol for placement of fine-wire electrodes into the neurovascular bundle of the hypoglossal nerve, using recognizable radiographic features and computerized axial tomography as guides. In these patients, while awake, optimal wire placement was associated with visible tongue protrusion without discomfort. With both surface stimulation and fine-wire FES, during sleep the stimulus intensity required to produce obvious electroencephalographic arousal was significantly greater than that producing a barely tolerable sensation while awake. During apneic events, the application of surface stimulation had an inconsistent effect, terminating 22% of the apneas, and fine-wire FES also had a limited impact, terminating 23% of the apneic events. We conclude from our studies that subjects tolerate surface and fine-wire FES to higher stimulus parameters during sleep than during wakefulness but that both approaches have an inconsistent effect on apneas during sleep.

Arterial oxygen saturation over time and sleep studies in quadriplegic patients.

This study evaluated arterial oxygen saturation (SaO2) over time in a randomly selected group of quadriplegic patients to assess whether clinical history prospectively correlated with profiles of oxygen saturation. In 16 stable male quadriplegic patients (C4-T5), we used pulse oximetry to measure SaO2 over a 24 hour period. Measured values of SaO2 were formatted into a cumulative frequency distribution of SaO2 over time. The cumulative SaO2 values from the quadriplegic patients were compared to SaO2 values in a control group of 12 age-matched healthy male subjects. Ten quadriplegic patients had SaO2 profiles comparable to the range observed in healthy subjects. Six quadriplegic patients had SaO2 profiles outside of the normative range. These 6 exhibited cyclic desaturations (> 4%) during periods of behaviorally-defined sleep, suggestive of sleep-disordered breathing. During wakefulness, however, their values of SaO2 were within the normative range. With respect to level of injury, age, time after injury, or medication use, there was no difference between the six 'hypoxic' quadriplegic patients and the 10 'normoxic' quadriplegic patients. Five of the 6 hypoxic patients had a positive medical history of snoring and increased daytime sleepiness, as compared to 6 of 10 normoxic patients who gave a similar history. We also performed polysomnographic studies in a subgroup of 7 quadriplegic patients. In this subgroup, sleep-disordered breathing was observed in 3 patients (AHI of 54/53/12 per hour, respectively). We conclude that in quadriplegic patients, in whom there is a low clinical suspicion for sleep-disordered breathing, there can occur significant decreases in SaO2 over time.

The nasal response to exercise in patients with cystic fibrosis.

This study has evaluated the nasal response to exercise in patients with cystic fibrosis (CF), a genetic disease in which factors such as chronic lung disease and/or nasal polyposis might be anticipated to modify nasal function responses. Measurements of nasal resistance (NAR) by posterior rhinomanometry and specific airway resistance (sRAW) were made before and 1, 5, 10, and 30 min after a 4-min period of exhausting legwork exercise (50% predicted maximal) in 19 CF patients (aged 11-29 years) and 10 healthy subjects (aged 11-31 years). One minute after exercise, healthy subjects showed a 54 +/- 5% (mean +/- SEM; standard error of the mean) relative fall from baseline in NAR and CF patients showed a 31 +/- 8% relative fall from baseline (p < 0.05). There were no significant differences in the magnitude or pattern of recovery in NAR after exercise (1 to 30 min) between the groups, largely because of the variability in NAR responses in CF patients. Exercise did not result in significant changes in sRAW in either group. We also found that a history or presence of nasal polyposis does not significantly affect functional nasal responses to exercise. Our conclusion is that the CF genotype and its airway sequelae do not substantively affect the control of the nasal response to exercise.

Extended monitoring of oxygen saturation in chronic lung disease.

The goal was to determine values of oxygen saturation from oximetry measurements over extended time periods in the context of prescribing or discontinuing supplemental oxygen. For group 1, when supplemental oxygen therapy was not in use, mean SpO2 values were significantly lower than when it was in use. Without supplemental oxygen, six of eight patients spent greater than 10 percent of the time at or below 88 percent saturation. For group 2, three of the nine patients spent 10 percent of the time at or below 88 percent SpO2. In 16 of 17 patients, lowest room air recorded values of SpO2 were less than 88 percent. We conclude that in many patients with chronic respiratory illness, prolonged monitoring of SpO2 will disclose the presence of hypoxemia. There may be substantial differences in health care cost and outcome depending upon the criteria chosen to prescribe or continue supplemental oxygen.

Serum erythropoietin levels and blood component therapy after autologous bone marrow transplantation: implications for erythropoietin therapy in this setting.

To determine the potential impact of recombinant human erythropoietin (EPO) therapy in patients undergoing autologous bone marrow transplantation (BMT) and colony-stimulating factor therapy, we assayed endogenous serum EPO levels and noted blood transfusion requirements in relapsed non-Hodgkin's lymphoma patients treated with high-dose chemo-radiation therapy and autologous BMT. Hematocrit and reticulocyte counts were determined daily, and hematocrit was maintained in the 25-30% range by transfusion according to criteria established by our hospital transfusion committee. EPO levels were measured by radioimmunoassay and were determined at baseline, throughout therapy, and 2 and 3 months after BMT. Serum EPO levels increased more than 25-fold above baseline in most subjects after initiating chemoradiation therapy. No correlation was noted between serum EPO and hematocrit, reticulocyte count or serum creatinine. Total red blood cell units transfused ranged from 4 to 15 (mean 7.7). Mean total donor exposures (red blood cell plus platelet units transfused) were 83.6 units (range 16-175). Serum EPO levels increased early in the course of preparation for autologous BMT and remained elevated for at least 2-3 weeks thereafter although at a lower level. Red blood cell transfusions were required despite very high EPO levels after BMT. Red cell transfusions, moreover, accounted for only 9.2% (69 of 746) of total donor exposures and only 5.8% (42 of 746) of donor exposures during the interval when pharmacologic doses of erythropoietin might be of benefit. In contrast to the potential benefit of colony-stimulating factors such as G-CSF and GM-CSF in BMT, our study suggests limited value for erythropoietin therapy in this setting.

Diurnal variations in serum erythropoietin levels in healthy subjects and sleep apnea patients.

We measured arterial oxygen saturation (SaO2) and serum erythropoietin (EPO) levels in patients with obstructive sleep apnea syndrome (OSAS) and in healthy subjects. SaO2 profile was analyzed as the cumulative distribution of SaO2 over time. OSAS patients spent 25.5 +/- 30.9% (SD) of the time at SaO2 of less than 88% vs. 0.64 +/- 1.6% in healthy subjects (P less than 0.05) and had 59 +/- 25 desaturations (greater than 4%) per hour vs. less than 5 per hour in healthy subjects (P less than 0.05). EPO measurements (radioimmunoassay) were made in blood samples withdrawn every 1 or 2 h over a 24-h period. The mean EPO concentration was higher (P less than 0.05) for OSAS patients (45 +/- 33 mU/ml) than for normal subjects (17 +/- 8 mU/ml). There was a significant variability in EPO values over the 24-h period. To analyze the EPO pattern over 24 h, EPO time series were fit to a general cosine function. Data from normal subjects conformed to a cosine function with an amplitude of 3.5 +/- 2.1 (CV of 60%) and an acrophase of 1,000 +/- 184 min after 0800 (CV of 18%), indicating a zenith about 1 A.M. and a nadir around 1 P.M. Data from OSAS subjects fit a similar cosine function with an amplitude of 19.9 +/- 41.0 (CV of 206%) and acrophase of 582 +/- 408 min (CV of 70%), indicating a greater variability in the magnitude and the timing of peak serum EPO levels.(ABSTRACT TRUNCATED AT 250 WORDS)