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At least 1,243 records · Page 69Linked to original sources
PubMed1995

Arthropathy, leucopenia and recurrent infection associated with a TcR gamma delta population.

This report documents the presence of clonal gamma delta T-cell receptor (TcR) population in the blood of a patient who presented with an arthropathy of undetermined cause, leucopenia and splenomegaly. There was no evidence for lymphoid malignancy clinically or at post-mortem. The phenotype and genotype of the clonal T-cell population were not associated with the predominant TcR delta rearrangement found in peripheral blood gamma delta cells, but were similar to those found in gamma delta TcR cells infiltrating rheumatoid synovium. The data indicate the presence of a monoclonal population of gamma delta cells TcR cells which in the face of continued immunosuppression behaved benignly. The case may represent a cytomorphologically atypical example of the large granular lymphocytes, neutropenia and arthropathy syndrome/lymphoproliferative disease of granular lymphocytes and, although the patient's clinical features were not 'classical', rheumatoid arthritis (RA) may have been the underlying primary disorder.

Arthralgia↗
PubMed2000

An investigation of interactions between the immune system and stimulus-secretion coupling in mouse submandibular acinar cells. A possible mechanism to account for reduced salivary flow rates associated with the onset of Sjögren's syndrome.

OBJECTIVES: To determine whether chronic exposure to lymphocyte-derived cytokines could inhibit the fluid secretory mechanism in salivary gland acinar cells and so account for the loss of gland function seen in the early stages of Sjögren's syndrome. METHODS: Mouse submandibular acinar cells maintained in primary culture were exposed to a profile of cytokines produced by concanavalin A-activated splenic lymphocytes in vitro for periods up to 72 h. Agonist-evoked changes in intracellular Ca(2+) were determined microfluorimetrically in both control and cytokine-treated cells. RESULTS: Acinar cells maintained in primary culture in the presence of cytokines for up to 72 h were able to mobilize intracellular calcium in response to stimulus by acetylcholine in an identical fashion to those maintained in primary culture in the absence of cytokines. Acute application of the conditioned medium produced by the activated lymphocytes had an antisecretory effect on acetylcholine-evoked Ca(2+) mobilization, which was found to be mediated by cholinesterase rather than by cytokines. CONCLUSION: Neither chronic nor acute exposure to the profile of cytokines released by concanavalin A-activated splenic lymphocytes interfered in any way with the second messenger cascade and fluid and electrolyte secretion in acinar cells. Our data suggest an alternative hypothesis, in which elevated levels of cholinesterase can metabolize acetylcholine released within the salivary glands and thus prevent fluid secretion.

Acetylcholine↗
PubMed2003

Natural killer cells in the synovial fluid of rheumatoid arthritis patients exhibit a CD56bright,CD94bright,CD158negative phenotype.

BACKGROUND: Natural killer (NK) cells play an important role in several animal models of autoimmunity by modulating T-cell responses, but it is unclear whether human NK cells have similar functions. METHODS: We characterized the phenotype of NK cells in synovial fluid (SF) and peripheral blood (PB) of patients with rheumatoid arthritis (RA) and in healthy control subjects using flow cytometry and quantitative PCR. RESULTS: The proportions of NK cells in PB and SF of RA patients were not significantly different from those in healthy PB. However, the SF NK cell phenotype was strikingly different, with increased CD94 and CD56 densities and greatly reduced proportions of cells expressing CD158a/b. These cells also had reduced mRNAs coding for CD158a/b and low perforin levels compared with RA PB and healthy PB NK cells. CONCLUSIONS: We identified a novel phenotype of SF NK cells that is of potential significance in RA. Experiments are now under way to determine the function of these SF NK cells and their potential role in RA.

Adult↗
PubMed2004

Hydroxychloroquine therapy in patients with primary Sjögren's syndrome may improve salivary gland hypofunction by inhibition of glandular cholinesterase.

OBJECTIVE: To determine whether (i) cholinesterase activity is increased in the saliva of patients with primary Sjogren's syndrome (pSS), (ii) increased levels of cholinesterase of lymphocyte origin could interfere with the secretory activity of submandibular acinar cells, and (iii) hydroxychloroquine at therapeutic doses could interfere with cholinesterase activity. METHODS: The Ellman method was used to determine the levels of salivary cholinesterase activity and the K(i) of both chloroquine and hydroxychloroquine for serum cholinesterase. The ability of lymphocyte cholinesterase to inhibit the acetylcholine (ACh)-evoked rise in [Ca(2+)](i) in mouse submandibular acinar cells was determined using fura-2 microfluorimetry. RESULTS: Patients with pSS had significantly higher levels of cholinesterase activity in both their unstimulated (P < 0.05) and stimulated saliva (P < 0.0001) compared with control subjects. Lymphocyte cholinesterase was capable of inhibiting the ACh-evoked rise in [Ca(2+)](i). The in vitro K(i) for hydroxychloroquine inhibition of cholinesterase was 0.38 +/- 1.4 microM. CONCLUSION: These data suggest that increased levels of cholinesterase present in the salivary glands of patients with pSS may contribute to glandular hypofunction and provide evidence that the therapeutic enhancement of salivary secretion in patients with pSS by hydroxychloroquine may be mediated by inhibition of glandular cholinesterase activity, although further in vivo investigation is needed.

Animals↗
PubMed2002

Preoperative factors associated with postoperative change in confusion assessment method score in hip fracture patients.

UNLABELLED: Postoperative delirium is a major problem in elderly patients undergoing surgical repair of hip fracture. It is imperative to identify potentially treatable preoperative factors associated with the onset of postoperative delirium to optimize outcome. We sought to determine what preoperative variables are associated with postoperative delirium in geriatric patients undergoing surgical repair of hip fracture. In a prospective, IRB-approved study, patients admitted to the geriatric hip fracture service were examined daily in the hospital for the occurrence of postoperative delirium. All patients with a preoperative diagnosis of dementia or delirium were eliminated. A positive confusion assessment method score ([+]CAM) was used to determine the presence of postoperative delirium during the acute hospital stay. To determine the association between preoperative variables (demographics, laboratory values, and comorbidities) and postoperative (+)CAM scores, chi(2) and logistic regression analysis were performed with calculation for the odds ratios (OR). One-hundred-sixty-eight patients (72% women) were included in the analysis. Twenty-eight percent (n = 47) of patients had a (+)CAM score. Three variables were significant predictors of a (+)CAM score: (a) normal white blood cell count (OR, 2.2), (b) abnormal serum sodium (OR, 2.4); and (c) ASA physical status >II (OR, 11.3). The results suggest that preoperative medical conditions (abnormal serum sodium and ASA physical status >II) and an inability to mount a stress response (normal white blood cell count) may influence the patient's postoperative mental status. In particular, two of the risk factors we identified may be amenable to therapy and are abnormal serum sodium and lack of an increase in white blood cell count during the stress of trauma and surgery. IMPLICATIONS: This prospective study investigated preoperative variables that are predictive of postoperative delirium in geriatric patients undergoing surgical repair of hip fracture. The results suggest that the patient's preoperative medical condition and inability to mount a stress response influence postoperative delirium.

Age Factors↗
PubMed2002

Expression of the chemokines MCP-1/JE and cytokine-induced neutrophil chemoattractant in early acute pancreatitis.

INTRODUCTION: Inflammatory mediators play a critical role in acute pancreatitis. The precise role played by members of the chemokine family remains unclear. AIMS: To investigate the expression of the CC chemokine monocyte chemotactic protein (MCP)-1/JE and the CXC chemokine cytokine-induced neutrophil chemoattractant (CINC) in early acute pancreatitis. METHODOLOGY: Pancreatitis was induced in rats, either by intraperitoneal injection of cerulein or by infusion of 5% sodium taurocholate into the pancreatic duct. Expression of MCP-1/JE and CINC in pancreas and plasma was determined by immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), Northern analysis, and quantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: Following induction of acute pancreatitis, MCP-1/JE and CINC immunoreactivity was seen in acinar cells. Infiltrating neutrophils were strongly immunolabeled with an anti-MCP-1/JE antibody, whereas macrophages reacted strongly with an antibody to CINC. Northern analysis and quantitative real-time RT-PCR demonstrated upregulation of MCP-1/JE and CINC mRNA levels in pancreatic tissue. Plasma MCP-1 levels were significantly increased after 6 hours in the cerulein hyperstimulation model (2,444 +/- 93 microg/mL versus control, 1,853 +/- 262 microg/mL; < 0.05). Plasma CINC levels were significantly increased after 6 hours in the cerulein hyperstimulation model (1,680 +/- 134 microg/mL versus control, 725 +/- 128 microg/mL; < 0.005) and after 3 hours in the bile salt infusion model (6,663 +/- 1,405 microg/mL versus control, 2,339 +/- 800 microg/mL; < 0.05). CONCLUSION: CINC and MCP-1/JE may be early mediators of the inflammatory response in acute pancreatitis.

Acute Disease↗
PubMed2002

Long-term follow-up of patients with serpinginous choroiditis.

PURPOSE: To evaluate the long-term clinical course of serpiginous choroiditis-a recurrent inflammatory disease that causes progressive visual loss-and to determine the efficacy of immunosuppressive therapy. METHODS: A retrospective study of patients who met inclusion criteria for serpiginous choroiditis at The University of Iowa Hospitals and Clinics was performed. Information collected included duration of follow-up, number of recurrences of inflammation, visual acuities, and development of choroidal neovascularization. The number of recurrences of inflammation in patients treated with immunosuppressive agents was compared with that in patients treated only with corticosteroids or observation. RESULTS: Seventeen patients were identified who had a mean age at presentation of 39.6 years. The mean duration of follow-up was 149.2 months, with 13 patients who were followed up for >60 months. Twelve eyes either presented with or developed macular choroidal neovascularization during follow-up. Thirteen of the patients were followed up for >12 months. Of these 13 patients, 6 received treatment with immunosuppressive agents along with corticosteroids. Four of the six patients developed no further inflammatory recurrence. Seven of the 13 patients were treated with corticosteroids or observation. All of these patients developed recurrences (P = 0.021, Fisher exact test). CONCLUSIONS: Immunosuppressive agents appear to reduce the rate of recurrent disease in serpiginous choroiditis compared with corticosteroids.

Adolescent↗
PubMed1999

The current role of surgery in the management of residual disease.

The increasing interest in surveillance rather than primary retroperitoneal lymph node dissection for clinical stage I testis cancer has led to retroperitoneal lymph node dissection being performed mostly after chemotherapy for stage II-IV disease. In most centres residual masses of 2-3 cm or more are removed; those smaller than this are most likely to be necrotic. The aim is to remove all residual disease even if this necessitates nephrectomy or excision of adjacent vascular structures. Laparoscopic approaches are hazardous in these circumstances. Thoraco-abdominal surgical approaches enable excellent access to retroperitoneal masses and synchronous excision of ipsilateral pulmonary metastases and thoracic lymph nodes. Retroperitoneal lymph node dissection also appears to be worthwhile in chemotherapy-resistant disease ('desperation retroperitoneal lymph node dissection'), although the relapse rate is higher in this group.

Humans↗
PubMed2005

Physician extenders impact trauma systems.

BACKGROUND: The implementation of revised surgical resident work hours has led many teaching hospitals to integrate health care extenders into the trauma service. We undertook this review to assess the effectiveness of these individuals in meeting the goals of the work hour restrictions and whether they impact other hospital and patient outcomes. METHODS: During the year 2002, we integrated two nurse practitioners into the trauma service of a teaching hospital. We prospectively collected data a year before (2001), during (2002), and a year after (2003) the integration that included number of admissions, hospital length of stay, intensive care stay, floor length of stay, mortality, direct cost per case, and weekly resident work hours on 44 residents at all levels. RESULTS: After the incorporation of physician extenders, we observed statistically significant reductions in floor, intensive care unit, and overall hospital lengths of stay. Patient mortality and cost per patient remained unchanged. Furthermore, we were able to obtain compliance with the Accreditation Council for Graduate Medical Education requirements for residency work hour limitations, as the average number of hours worked per resident on the trauma service decreased from 86 hours to 79 hours per week. CONCLUSION: As graduate medical education becomes ever more regulated, physician extenders can be successfully integrated into busy academic Level I trauma centers. This integration positively impacts patient flow and resident work hours without altering patient outcomes or direct hospital cost.

Academic Medical Centers↗
PubMed2005

Trauma/critical care surgeon: a specialist gasping for air.

BACKGROUND: In the last 10 years, trauma/critical care has become less attractive because of the decreasing surgical caseload, the nocturnal work hours, and the economics of the practice. Nevertheless, during the same period, the number of verified trauma centers has significantly increased. This study assesses the economic drive behind this dichotomy. METHODS: Over a 1-year period, we collected financial data on 1,907 trauma patients for both Level I trauma centers and trauma/critical care surgeons. Financial data, including payor source, cost, reimbursement, margin, and reimbursement-to-charge and reimbursement-to-direct cost ratios, were calculated. RESULTS: For commercial- and government-insured patients, the reimbursement-to-direct cost ratio was 2-and 35-fold greater, respectively, for the trauma centers than for the trauma/critical care surgeons. For uninsured patients, the addition of local government funds allowed the trauma center to cover direct cost with no margin. In contrast, even with the addition of supplemental salary dollars from the institution, for every dollar in direct cost generated by the trauma/critical care surgeons in caring for uninsured patients, they recovered 55 cents, or a loss of 45 cents per direct cost dollar spent. CONCLUSION: The economic dichotomy that exists between trauma centers and trauma/critical surgeons is significant. It drives institutional growth and, at the same time, discourages surgeons from entering the subspecialty. As physician reimbursement decreases and the number of uninsured patients increases, this economic dichotomy will amplify. Over the next decade, without a significant adjustment, the subspecialty is in danger of extinction.

Career Choice↗
PubMed2005

Mixed lymphocyte cultures can predict TCR Vbeta repertoires of T cells infiltrating kidney transplants during acute rejection episodes.

Alloreactive T cell populations can show skewing of T-cell antigen receptor (TCR) Vbeta gene usage. The aims of the experiments were to compare in vivo and in vitro T cell alloresponses against donor alloantigens for TCR Vbeta gene usage. T-cell cultures from renal biopsies taken during acute rejection and pretransplant mixed lymphocyte cultures (MLC) were established from five renal transplant patients. TCR Vbeta gene usage, assessed with Vbeta family specific antibodies, showed that up to five different Vbeta families were significantly expanded. In four of five cases, there was close concordance between Vbeta families expanded from the biopsy and in MLC. T-cell clones from one renal biopsy were specific for the mismatched donor alloantigen and showed similar TCR Vbeta gene usage to the original T-cell line. The results show very similar patterns of TCR Vbeta gene usage in alloreactive T cells generated ex vivo or in vitro.

Acute Disease↗
PubMed2005

Fast robust correlation.

A new, fast, statistically robust, exhaustive, translational image-matching technique is presented: fast robust correlation. Existing methods are either slow or non-robust, or rely on optimization. Fast robust correlation works by expressing a robust matching surface as a series of correlations. Speed is obtained by computing correlations in the frequency domain. Computational cost is analyzed and the method is shown to be fast. Speed is comparable to conventional correlation and, for large images, thousands of times faster than direct robust matching. Three experiments demonstrate the advantage of the technique over standard correlation.

Algorithms↗