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1.
Int J Emerg Med ; 16(1): 58, 2023 Sep 13.
Article in English | MEDLINE | ID: mdl-37704957

ABSTRACT

BACKGROUND: This study examined the conflicts between different generations working in US emergency departments (ED). We sought to record generational differences involving communication preferences, perceived areas of conflict, work motivations, and attitudes regarding work-life balance. METHODS: We developed a survey to assess the physician perspective on generational conflict in the ED. The survey was distributed to members of the American College of Emergency Physicians, a professional organization comprising emergency medicine physicians in the USA. RESULTS: We received 696 completed responses. Men represented 60% of respondents and the largest proportion of respondents were emergency physicians working in community settings (53%); 11% were residents. Generation representation was smallest for Traditionalist (2%) and largest for Gen X (43%). Seventy percent reported observing conflict due to generational communication with the largest frequency being once a week (26%). In the associated open-ended questions, 247 (33%) provided 316 anecdotal descriptions of observed conflict. Responses clustered into seven themes (ordered by frequency): Work Ethic, Treatment Approach, Technology Application, Entitlement, Professionalism, Work Life/Balance, and Communication Style. Comparing Work Ethic responses, 52-70-year-olds reported that younger providers are less interested in "accomplishing anything" while 26-34-year-olds resented that attitude. Respondents completing the open-ended questions regarding preventing and responding to conflict provided some insight into helpful strategies including actions supportive of clear communication and standardized policies and expectations. Only 5% of respondents reported that they had discussed generational communication in department meetings with the odds of a woman reporting conflict being less than males (p = .01). CONCLUSION: Conflicts in the ED in the USA can be attributed to how an individual views the values of someone from another generation. Understanding the frequency and areas of generational conflict in the ED can help medical leaders find strategies to mitigate negative workplace interactions.

2.
Clin Pract Cases Emerg Med ; 7(3): 165-167, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37595304

ABSTRACT

INTRODUCTION: Weakness is a common symptom that within itself does not indicate a specific diagnosis. Recreational inhalant use such as nitrous oxide (NO) may not often be disclosed. Additionally, professional or occupational history, such as being a dentist or dental assistant, should be determined because of higher reported rates of NO misuse. Nitrous oxide can cause vitamin B12 deficiency and resulting neuropathy. Nitrous oxide toxicity can have a wide variation of presentations with or without laboratory abnormalities or remarkable imaging findings, which can further complicate a diagnosis of weakness secondary to NO use. CASE REPORT: A 33-year-old female presented to the emergency department with progressive bilateral leg numbness and objective weakness after repeated recreational NO use. After an extensive workup, she was found to have vitamin B12 deficiency and an electromyography study consistent with myeloneuropathy, despite normal imaging. She was prescribed high-dose vitamin B12 therapy and stopped using NO. One year after diagnosis, our patient maintained NO sobriety and had near-complete resolution of prior neurologic deficits. CONCLUSION: The use of recreational inhalant and the patient's occupation should be considered when a patient presents with weakness. Obtaining vitamin B12 and methylmalonic acid levels should be considered for diagnosis. However, NO-induced neuropathy can be seen in patients with normal vitamin B12 and methylmalonic levels and patients do not always have abnormal imaging findings. The healthcare team should consider the varied presentations and findings of substance-induced conditions such as NO toxicity.

3.
Cureus ; 14(11): e31461, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36523662

ABSTRACT

Elderly patients are often considered poor surgical candidates for intra-thoracic operations due to the number of comorbidities, increased risks associated with general anesthesia, decreased cardiopulmonary reserve, and overall increased frailty. In addition, coronavirus disease 2019 (COVID-19) is a critical psychosocial factor that, through secondary effects, can prevent patients from receiving optimal care. Patients are reduced to having limited contact with family, often a vital support system, which can contribute to feelings of hopelessness, loneliness, and depression. We report the case of a 95-year-old female who presented to the emergency department with increasing supplemental oxygen requirements two weeks after a ground-level fall. She was found to have multiple rib fractures and a left-sided hemothorax. Initial management included aggressive respiratory therapy, multiple pigtail chest tubes, and thrombolytics; however, these measures failed to drain the intrathoracic hematoma. Her care was complicated by the psychosocial and isolation factors of COVID-19 which led to the patient exhibiting symptoms of hopelessness, grief, lack of appetite, and loneliness. As conservative management did not improve her clinical care the patient required a video-assisted thoracoscopic surgery (VATS) to manage the retained hemothorax and facilitate re-expansion of her atelectatic lung. Once the patient was removed from COVID-19 precautions, she was taken to surgery and postoperatively the patient reported minimal pain, participated more in physical therapy, and increased her oral intake. In this unique case, a 95-year-old patient with a hemothorax that was successfully treated with a VATS had her clinical care complicated by the psychosocial implications of COVID-19.

4.
Cureus ; 14(12): e32871, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36699751

ABSTRACT

PURPOSE: Given the advancements in dissection modalities over the last decade, what is the current understanding of the alar fascia and its clinical implications as an access point into the danger space (DS)? The aim of the study is to provide an updated review of the alar fascia and danger space. METHODS: A comprehensive search of the alar fascia and danger space was performed through PubMed databases up to August 2022. Thirty-two sagittal E12 sheet plastination slices of the head and neck were analyzed under a stereomicroscope to assess the morphology and continuity of the retropharyngeal, alar, and prevertebral fasciae (PVF and their respective potential spaces). RESULTS: Recent advancements have provided evidence that the alar fascia is a true fascial layer between the retropharyngeal and danger spaces within the deep cervical region. Although its composition, histological features, and borders remain topics of controversy, the alar fascia is comprised of dense connective tissue and may serve as a physical barrier to prevent the spread of infection into the danger space. Complications arising from deep neck infections that invade the danger space include mediastinitis, necrotizing fasciitis, and empyema. CONCLUSION: A proper understanding of the anatomy, structure, function, and potential spaces is crucial to assessing the alar fascia and danger space routinely in clinical practice, especially when imaging.

5.
Clin Toxicol (Phila) ; 59(10): 913-917, 2021 Oct.
Article in English | MEDLINE | ID: mdl-33688774

ABSTRACT

STUDY PURPOSE: With increasing state legalization, marijuana use has become commonplace throughout much of the United States. Existing literature on unintentional exposure focuses primarily on children.We report on a cluster of adults with unwitting marijuana exposure. METHODS: A cluster of cases were referred to the Medical Toxicology Service after ingesting marijuana-contaminated food at a family event. We conducted a retrospective analysis of twelve subject charts and a qualitative analysis with six of these subjects who willingly consented to be interviewed about their experiences. The study was approved by the Institutional Review Board. RESULTS: Three of the subjects (25%) required prolonged observation due to persistent symptoms. Eleven (92%) were urine immunoassay positive for tetrahydrocannabinol (THC). Two subjects (17%) tested positive for ethanol in their blood. Common symptoms experienced by the subjects included confusion (50%), difficulty speaking (67%), nausea (25%), tremors (17%), and feelings of unreality (33%). All interviewed subjects reported sleepiness and three (50%) reported a negative impact on work. Subjects also reported multiple emotions, including anger, confusion, disbelief, and helplessness. None of the cases resulted in admission for critical care or death. CONCLUSIONS: Our series illuminates effects of unwitting and/or unintentional marijuana exposure in adults. Unintentional marijuana poisonings have increased, but legal and regulatory barriers have limited the study of marijuana outside highly controlled conditions. While the marijuana exposure in this study did not result in admission for critical care or death, it did result in psychological distress and adversely affected work in some cases.


Subject(s)
Cannabis/poisoning , Food Contamination , Illicit Drugs/poisoning , Poisoning/etiology , Adult , Aged , Biomarkers/urine , Dronabinol/urine , Female , Humans , Male , Middle Aged , Poisoning/diagnosis , Poisoning/physiopathology , Poisoning/psychology , Prognosis , Retrospective Studies , United States , Urinalysis , Young Adult
6.
Acad Emerg Med ; 26(5): 539-548, 2019 05.
Article in English | MEDLINE | ID: mdl-30240039

ABSTRACT

OBJECTIVES: We wanted to estimate the frequency and describe the nature of emergency department (ED) procedural sedation restrictions in the State of California. METHODS: We surveyed medical directors for all licensed EDs statewide regarding limitations on procedural sedation practice. Our primary outcome was the frequency of restrictions on procedural sedation, defined as an inability to administer moderate sedation, deep sedation, and typical ED sedative agents in accordance with American College of Emergency Physicians (ACEP) guidelines. Our secondary outcomes were the nature of these restrictions, who has imposed them, why they were imposed, and the perceived clinical impact. RESULTS: We obtained responses from 211 (64%) of the 328 EDs. Ninety-one (43%) reported conditional or total limitations on their ability to administer one or more of the following: moderate sedation, deep sedation, propofol, ketamine, or etomidate. Thirty-nine (18%) reported total restriction of at least one of these-most frequently a prohibition of deep sedation (18%). Local anesthesia directors were the most frequently cited creators and enforcers of these restrictions. Some respondents reported that, due to these restrictions, they used less effective sedatives, they performed procedures without sedation when sedation would have been preferred, and they observed inadequate sedation and pain control. CONCLUSIONS: In this statewide survey we found a substantial prevalence of practice limitations-mostly created by local anesthesia directors-that restrict the ability of emergency physicians to provide procedural sedation for their patients in accordance with ACEP guidelines. Deep sedation was prohibited in 18% of responding EDs. Our respondents describe adverse consequences to patient care.


Subject(s)
Conscious Sedation/standards , Deep Sedation/standards , Emergency Service, Hospital/standards , California , Emergency Medicine/legislation & jurisprudence , Emergency Service, Hospital/statistics & numerical data , Etomidate/administration & dosage , Female , Humans , Hypnotics and Sedatives/administration & dosage , Ketamine/administration & dosage , Male , Propofol/administration & dosage , Surveys and Questionnaires
7.
West J Emerg Med ; 18(4): 770-774, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28611900

ABSTRACT

INTRODUCTION: A dislodged gastrostomy tube (GT) is a common complaint that requires evaluation in the pediatric emergency department (ED) and, on occasion, will require stoma dilation to successfully replace the GT. The objective of this study was to describe the frequency that stoma dilation is required, the success rate of replacement, complications encountered, and the techniques used to confirm placement of the GT after dilation. METHODS: We conducted a retrospective medical record review of children 0-18 years who presented to the pediatric ED from February 2013 through February 2015 with a dislodged GT that required stoma dilation by pediatric emergency physicians with serially increasing Foley catheter sizes prior to successful placement of the GT. RESULTS: We reviewed a total of 302 encounters in 215 patients, with 97 (32%) of the encounters requiring stoma dilation prior to replacing a GT. The median amount of dilation was 2 French between the initial Foley catheter size and the final GT size. There was a single complication of a mal-positioned balloon that was identified at the index visit. No delayed complications were encountered. We performed confirmation of placement in all patients. The two most common forms of confirmation were aspiration of gastric contents (56/97 [58%]) followed by contrast radiograph in 39 (40%). CONCLUSION: The practice of serial dilation of a gastrostomy stoma site to allow successful replacement of a gastrostomy tube in pediatric patients who present to the ED with a dislodged gastrostomy tube is generally successful and without increased complication. All patients received at least one form of confirmation for appropriate GT placement with the most common being aspiration of gastric contents.


Subject(s)
Catheters, Indwelling/adverse effects , Dilatation/methods , Equipment Failure , Gastrostomy/adverse effects , Gastrostomy/instrumentation , Surgical Stomas/adverse effects , Adolescent , Child , Child, Preschool , Emergency Service, Hospital , Humans , Pediatric Emergency Medicine , Reoperation , Retrospective Studies
8.
Ann Emerg Med ; 68(4): 409-18, 2016 10.
Article in English | MEDLINE | ID: mdl-27181080

ABSTRACT

STUDY OBJECTIVE: In 2001, less than 20% of emergency medicine residents had more than $150,000 of educational debt. Our emergency medicine residents anecdotally reported much larger debt loads. Surveys have reported that debt affects career and life choices. Qualitative approaches are well suited to explore how and why such complex phenomena occur. We aim to gain a better understanding of how our emergency medicine residents experience debt. METHODS: We conducted individual semistructured interviews with emergency medicine residents. We collected self-reported data related to educational debt and asked open-ended questions about debt influence on career choices, personal life, future plans, and financial decisions. We undertook a structured thematic analysis using a qualitative approach based in the grounded theory method. RESULTS: Median educational debt was $212,000. Six themes emerged from our analysis: (1) debt influenced career and life decisions by altering priorities; (2) residents experienced debt as a persistent source of background stress and felt powerless to change it; (3) residents made use of various techniques to negotiate debt in order to focus on day-to-day work; (4) personal debt philosophy, based on individual values and obtained from family, shaped how debt affected each individual; (5) debt had a normative effect and was acculturated in residency; and (6) residents reported a wide range of financial knowledge, but recognized its importance to career success. CONCLUSION: Our emergency medicine residents' debt experience is complex and involves multiple dimensions. Given our current understanding, simple solutions are unlikely to be effective in adequately addressing this issue.


Subject(s)
Education, Medical/economics , Emergency Medicine/education , Financing, Personal/economics , Internship and Residency/economics , Adult , California , Career Choice , Emergency Medicine/economics , Female , Humans , Interviews as Topic , Male , Qualitative Research , Workforce
9.
Emerg Med J ; 33(8): 548-52, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27002161

ABSTRACT

BACKGROUND: We hypothesised the addition of brief empathetic statements to physician-patient interaction might decrease thoughts regarding litigation. METHODS: We enrolled a convenience sample of adults in our emergency department (ED) waiting room into a randomised, double-blind controlled trial. Subjects watched videos of simulated discharge conversations between physicians and patient actors; half of the videos differed only by the inclusion of two brief empathetic statements: verbalisations that (1) the physician recognises that the patient is concerned about their symptoms and (2) the patient knows their typical state of health better than a physician seeing them for the first time and did the right thing by seeking evaluation. After watching the video subjects were asked to score a five-point Likert scale their thoughts regarding suing this physician in the event of a missed outcome leading to lost work (primary outcome), and four measures of satisfaction with the physician encounter (secondary outcomes). RESULTS: We enrolled and randomised 437 subjects. 213 in the empathy group and 208 in the non-empathy group completed the trial. Sixteen subjects did not complete the trial due to computer malfunction or incomplete data sheets. Empathy group subjects reported statistically significant less thoughts of litigation than the non-empathy group (mean Likert scale 2.66 vs 2.95, difference -0.29, 95% CI -0.04 to -0.54, p=0.0176). All four secondary measures of satisfaction with the physician encounter were better in the empathy group. CONCLUSIONS: In this study, the addition of brief empathetic statements to ED discharge scenarios was associated with a statistically significant reduction in thoughts regarding litigation. CLINICAL TRIAL REGISTRATION: NCT01837706.


Subject(s)
Empathy , Jurisprudence , Patients/psychology , Physician-Patient Relations , Adolescent , Adult , Aged , Double-Blind Method , Emergency Service, Hospital , Female , Humans , Male , Middle Aged , Patient Satisfaction , Prospective Studies , Video Recording
10.
Cell Transplant ; 24(1): 11-23, 2015.
Article in English | MEDLINE | ID: mdl-24143907

ABSTRACT

Better results have been recently reported in clinical pancreatic islet transplantation (ITX) due mostly to improved isolation techniques and immunosuppression; however, some limitations still exist. It is known that following transplantation, 30% to 60% of the islets are lost. In our study, we have investigated 1) the role of size as a factor affecting islet engraftment and 2) potential procedural manipulations to increase the number of smaller functional islets that can be transplanted. C57/BL10 mice were used as donors and recipients in a syngeneic islet transplant model. Isolated islets were divided by size (large, >300 µm; medium 150-300 µm; small, <150 µm). Each size was transplanted in chemically induced diabetic mice as full (600 IEQ), suboptimal (400 IEQ), and marginal mass (200 IEQ). Control animals received all size islets. Engraftment was defined as reversal of diabetes by day 7 posttransplantation. When the superiority of smaller islets was observed, strategies of overdigestion and fragmentation were adopted during islet isolation in the attempt to reduce islet size and improve engraftment. Smaller islets were significantly superior in engraftment compared to medium, large, and control (all sizes) groups. This was more evident when marginal mass data were compared. In all masses, success decreased as islet size increased. Once islets were engrafted, functionality was not affected by size. When larger islets were fragmented, a significant decrease in islet functionality was observed. On the contrary, if pancreata were slightly overdigested, although not as successful as small naive islets, an increase in engraftment was observed when compared to the control group. In conclusion, smaller islets are superior in engraftment following islet transplantation. Fragmentation has a deleterious effect on islet engraftment. Islet isolations can be performed by reducing islet size with slight overdigestion, and it can be safely adopted to improve clinical outcome.


Subject(s)
Diabetes Mellitus, Experimental , Graft Survival , Islets of Langerhans Transplantation , Islets of Langerhans/pathology , Animals , Diabetes Mellitus, Experimental/pathology , Diabetes Mellitus, Experimental/surgery , Male , Mice , Organ Size , Transplantation, Isogeneic
11.
Wilderness Environ Med ; 25(2): 198-203, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24864067

ABSTRACT

We report 2 cases of catastrophic ischemic stroke after Crotalidae polyvalent immune Fab (ovine)-treated rattlesnake envenomation, 1 fatal and the other resulting in significant permanent disability. It is possible these serious adverse events may have been related to venom factor(s), an interaction between venom and antivenom, occult patient blood dyscrasia, or to random unrelated events. We present the rationale for each possibility, and submit the experiences to elicit alternate postulation and communication of similar presentations.


Subject(s)
Antivenins/adverse effects , Immunoglobulin Fab Fragments/adverse effects , Snake Bites/drug therapy , Stroke/chemically induced , Stroke/physiopathology , Adolescent , Animals , Antivenins/therapeutic use , Crotalus , Humans , Immunoglobulin Fab Fragments/therapeutic use , Male , Middle Aged
12.
Wilderness Environ Med ; 25(1): 80-1, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24412661

ABSTRACT

Priapism in children after a black widow spider bite is a rare phenomenon with only a few case reports noted in the literature. Black widow bites are commonly associated with pain, muscle cramping, hypertension, and tachycardia. Initial treatment includes pain control with opiate or opioid medications and benzodiazepines, with antivenom reserved for severe cases of envenomation manifested by uncontrolled pain or hypertension. Treatment with antivenom for priapism is not well described; however, it has been noted to resolve priapism in the few cases that have been reported. We present a case of a 3-year-old boy who was bitten by a black widow and presented with abdominal cramping and priapism.


Subject(s)
Black Widow Spider , Priapism/drug therapy , Spider Bites/complications , Abdominal Pain/drug therapy , Animals , Antivenins/therapeutic use , Child, Preschool , Humans , Male , Priapism/etiology , Spider Bites/drug therapy
13.
Transplantation ; 95(7): 919-27, 2013 Apr 15.
Article in English | MEDLINE | ID: mdl-23545505

ABSTRACT

BACKGROUND: KRP203, a structural FTY720 analogue, has 5-fold greater selectivity for binding to sphingosine-1-phosphate receptor (S1PR) 1 (S1PR(1)) versus S1PR3 and 100-fold greater selectivity over S1PR(2) and S1PR(5). Although the immunoregulatory effects of FTY720 have been tested in clinical and experimental research, the therapeutic efficacy of KRP203 in allograft models remains elusive. In this study, we investigated the potential of KRP203 alone and in combination with intragraft injection of CD4(+)CD25(+)FoxP3(+) regulatory T cells (Tregs) to induce islet allograft tolerance. METHODS: BALB/c (H-2(d)) mice received transplants of fresh C57BL/10 (H-2(b)) islet allografts under the kidney capsule and were treated for 7 days with 0.3, 1.0, or 3.0 mg/kg KRP203 alone or in combination with intragraft-infused Tregs. RESULTS: Untreated BALB/c mice acutely rejected C57BL/10 islet allografts at a mean survival time of 13.8 ± 2.7 days (n=5). A 7-day dosing of 0.3 or 1.0 mg/kg KRP203 produced long-term islet allograft survival (9200 days) in one of five and two of seven recipients, respectively. A 3 mg/kg KRP203 dose resulted in islet graft survival for more than 200 days in 5 of 12 recipients. Whereas recipients that received 500 allogeneic islets admixed with 5 x 10(5) - 7 x 10(5) Tregssurvived 83.6 ± 67.2 days, addition of transient 3 mg/kg KRP203 therapy induced prolonged drug-free graft survival (9200 days) in all recipients. CONCLUSIONS: A brief treatment with KRP203 significantly prolonged islet allograft survival, whereas additional intragraft delivery of Tregs induced tolerogenic effects selective to islet alloantigens.


Subject(s)
Adoptive Transfer , Graft Rejection/prevention & control , Graft Survival/drug effects , Immunosuppressive Agents/pharmacology , Islets of Langerhans Transplantation/immunology , Receptors, Lysosphingolipid/drug effects , Sulfhydryl Compounds/pharmacology , T-Lymphocytes, Regulatory/transplantation , Animals , Biomarkers/metabolism , Cells, Cultured , Combined Modality Therapy , Dose-Response Relationship, Drug , Forkhead Transcription Factors/genetics , Forkhead Transcription Factors/metabolism , Graft Rejection/immunology , Graft Rejection/metabolism , Green Fluorescent Proteins/genetics , Green Fluorescent Proteins/metabolism , Interleukin-2 Receptor alpha Subunit/metabolism , Islets of Langerhans Transplantation/adverse effects , Mice , Mice, Inbred BALB C , Mice, Inbred C3H , Mice, Inbred C57BL , Mice, Transgenic , Receptors, Lysosphingolipid/metabolism , Sphingosine-1-Phosphate Receptors , T-Lymphocytes, Regulatory/immunology , Time Factors , Transplantation Tolerance/drug effects
14.
Toxicon ; 69: 29-37, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23474267

ABSTRACT

BACKGROUND: In patients bitten by North American rattlesnakes and treated with Crotalidae Polyvalent Immune Fab (Ovine) (FabAV), late hematologic abnormalities-persistent, recurrent, or late, new onset of hypofibrinogenemia, prolonged PT/INR, prolonged PTT, and/or thrombocytopenia beyond 48 h post-envenomation-are common, difficult to manage, and may result in morbidity and mortality are common, difficult to manage, and may result in morbidity and mortality. The optimal management of late hematologic abnormalities, particularly the use of further treatment with antivenom, has not been well defined. The current FabAV treatment regimen is to give antivenom as a bolus dose over a one-hour period. We describe our experience using a continuous intravenous infusion of FabAV for late hematologic effects and/or associated bleeding complications in rattlesnake envenomation. METHODS: This is a retrospective, observational case series of patients envenomated by North American rattlesnakes at three medical centers managed with a continuous intravenous infusion of FabAV for late hematologic abnormalities and/or associated bleeding complications. Indications, dilution and infusion protocols, and duration of therapy were individualized. RESULTS: Five cases were identified between July 2010 and September 2011. All patients had profound late hematologic abnormalities and/or were associated with bleeding complications. Several patients had received repeat bolus infusions of FabAV, with or without human blood products, with either inadequate or only transient beneficial response. All patients were then managed with a continuous intravenous infusion of FabAV and all appeared to respond to the continuous intravenous infusion of FabAV, titrated to effect, with cessation of progression and, in most cases, improvement in hematologic abnormalities. Rates of infusion varied from 2 to 4 vials per 24 h (mean = 3.1 ± 0.4 vials/day). The termination of FabAV infusion was between day 6 and day 14 from the time of envenomation (mean = 10 ± 3 days), after which hematologic values were normalized or were normalizing in all patients and continued to do so. DISCUSSION: The use of FabAV as a continuous intravenous infusion, particularly after the acute phase of envenomation has passed, provides a continuous source of circulating antibodies to neutralize venom components reaching circulation from tissue stores and allows natural replenishment of hematologic factors such as platelets and/or fibrinogen. This method is an efficient use of FabAV, avoiding the wasteful excess of a bolus dose, may be more effective, eliminating the potential for destruction of hematologic factors when protective antivenom levels are lost between bolus FabAV doses, and appears to be safe. Further assessments of the stability and sterility of the product during infusion are needed. The need to continue hospitalization is the major drawback, but continued observation and inpatient care may be needed for other indications (e.g. bleeding) in this subset of patients. CONCLUSIONS: A continuous intravenous infusion of FabAV between 2 and 4 vials per day, titrated to effect, and continued for 6-14 days post-envenomation appeared to be associated with reversal of late hematologic effects of rattlesnake envenomation and, when combined with indicated human blood products, control of significant bleeding. Continuous intravenous infusion of FabAV may be safer, more efficacious, and more cost-effective than observation without FabAV treatment or as-needed bolus dosing in selected patients with late hematologic abnormalities.


Subject(s)
Antivenins/therapeutic use , Immunoglobulin Fab Fragments/therapeutic use , Snake Bites/drug therapy , Adolescent , Adult , Aged , Animals , Blood Coagulation Disorders/drug therapy , Crotalus , Female , Hemorrhage/drug therapy , Humans , Infusions, Intravenous , Male , Middle Aged , Retrospective Studies , Thrombocytopenia/drug therapy , Treatment Outcome , United States
15.
Transplantation ; 82(12): 1756-63, 2006 Dec 27.
Article in English | MEDLINE | ID: mdl-17198272

ABSTRACT

BACKGROUND: Previously we showed that pancreatic islets cultured for seven days in rotating bioreactors survived for >100 days in allogeneic recipients without immunosuppression. This survival coincided with almost complete elimination of "passenger" donor dendritic cells (DCs). Herein, we examined the necessity of DCs in the generation of CD4+ CD25+ T regulatory (Treg) cells. METHODS: Allogeneic fresh islets or islets cultured for three days in bioreactors were transplanted to streptozotocin-induced diabetic Balb/c(stat4 -/-) as well as signal transducers and activators of transcription (Stat)4-deficient Balb/c(stat6 -/-) or Balb/c(stat4 -/-) mice. Some Balb/c recipients of fresh islet allografts were also treated with a tolerogenic protocol of anti-CD40 Ligand MR1 mAb and CTLA4Ig. RESULTS: Islet allografts cultured for three days in bioreactors survived >100 days in all Balb/c(stat4 -/-) recipients and in 56% of Balb/c(stat6 -/-) recipients, but in none of the Balb/c recipients; the same recipients rejected fresh islet allografts. Purified T cells from long-term surviving Balb/c(stat4 -/-) recipients failed to transfer tolerance to SCID recipients of donor-type fresh islet allografts. In contrast, MR1/CTLA4Ig therapy induced tolerance to fresh islet allografts and their T cells adoptively transferred tolerance. When Balb/c or Balb/c(stat4 -/-) recipients of bioreactor-cultured islets were injected intravenously with immature syngeneic DCs, they became tolerant and developed potent alloantigen-specific CD4+ CD25+ Treg cells expressing Foxp3. CONCLUSION: Allogeneic islets depleted of donor DCs by culture in bioreactors have almost twofold better acceptance in Balb/c(stat4 -/-) than in Balb/c(stat6 -/-) mice, but lack Treg cells. Additional injection of host immature DCs improves tolerance in Balb/c and Balb/c(stat4 -/-) recipients by inducing potent CD4+ CD25+ Treg cells.


Subject(s)
Culture Techniques , Dendritic Cells/immunology , Islets of Langerhans Transplantation/immunology , T-Lymphocytes, Regulatory/immunology , Transplantation Tolerance , Animals , Bioreactors , CD4 Antigens/analysis , Graft Survival/genetics , Interleukin-2 Receptor alpha Subunit/analysis , Islets of Langerhans/cytology , Islets of Langerhans/immunology , Mice , Mice, Mutant Strains , STAT4 Transcription Factor/deficiency , STAT4 Transcription Factor/genetics , STAT6 Transcription Factor/deficiency , STAT6 Transcription Factor/genetics , Tissue Donors , Transplantation, Homologous , Weightlessness
16.
Transplantation ; 74(1): 13-21, 2002 Jul 15.
Article in English | MEDLINE | ID: mdl-12134093

ABSTRACT

BACKGROUND: The failure of pancreatic islet allotransplants observed in almost all clinical attempts is related to poor initial islet function and allograft rejection. To remedy these problems we cultured islets in microgravity conditions to improve their function and to reduce their immunogenicity. METHODS: Fresh mouse islets or mouse islets cultured in stationary dishes or microgravity bioreactors were transplanted to streptozotocin-induced diabetic mouse recipients. RESULTS: Both allogeneic dish- or bioreactor-cultured islets survived more than 100 days compared with fresh allogeneic islets, which were rejected in less than 15 days. Islet titration studies revealed that 250 fresh or dish-cultured, but only 30 to 120 bioreactor-cultured, islets were necessary to produce euglycemia. Furthermore, glucose tolerance tests showed that bioreactor-cultured islets functioned better compared with fresh and dish-cultured islets on day 30 postgrafting. Immunostaining and transmission electron microscopy (TEM) analyses showed the gradual disappearance of dendritic cells in cultured islets compared with fresh islets. TEM revealed that the ultrastructure of islets from bioreactor, but not dish, appeared healthy and closely resembled fresh islets. Interestingly, TEM and scanning electron microscopy showed that only bioreactor-cultured islets developed unique and multiple nutritional channels between arrays of islet cells. TEM with colloidal lanthanum tracer revealed that only bioreactor islet cell cultures were devoid of tight junctional complexes, which may facilitate channel formation. CONCLUSION: Microgravity condition decreases immunogenicity and significantly improves the function of secretory cells.


Subject(s)
Cell Culture Techniques/methods , Islets of Langerhans Transplantation/methods , Islets of Langerhans/immunology , Islets of Langerhans/ultrastructure , Weightlessness Simulation , Animals , Biological Transport/physiology , Bioreactors , Dendritic Cells/cytology , Dendritic Cells/immunology , Diabetes Mellitus, Experimental/surgery , Graft Survival/immunology , Histocompatibility Antigens Class II/analysis , Islets of Langerhans/metabolism , Islets of Langerhans Transplantation/immunology , Mice , Mice, Inbred C3H , Mice, Inbred C57BL , Microscopy, Electron , Microvilli/ultrastructure , Transplantation, Homologous
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