The Impact of Dopamine on Hemodynamics,Oxygen Metabolism,and Cerebral Resuscitation After Restoration of Spontaneous Circulation in Pigs

Background: Restoration of spontaneous circulation after cardiopulmonary resuscitation in cardiac arrest patients does not always signal a completely successful outcome. Functional deficiencies of the nervous system are found in many survivors of cardiac arrest. Objectives: To study the effects of dopamine-induced elevated blood pressure on the hemodynamics, oxygen metabolism, and cerebral resuscitation in different perfusion conditions in a resuscitated animal model. Methods: There were 18 pigs included in the study. Ventricular fibrillation (VF) was induced with a programmed electrical stimulation device. After 4 min of untreated ventricular fibrillation followed by 9 min of CPR, 12 animals were resuscitated successfully, and were then randomly assigned to either the study group (dopamine group) or the control group (normal perfusion group). All animals in the two groups received normal saline through continuous intravenous guttae for 4 h at a rate of 15 mL/kg/h. In the study group, dopamine was added to raise the animals' blood pressure. Four hours of intensive monitoring was performed for all study animals. Finally, 24-h evaluation of neurological function was conducted in surviving animals in accordance with the standard of the Cerebral Performance Category Score. Results: In animals in the dopamine group, the cardiac output, mean aortic pressure, coronary perfusion pressure, oxygen delivery, and oxygen consumption were higher than those found in the animals in the normal perfusion group (p < 0.05). Oxygen metabolism was remarkably improved in animals in the dopamine group. Furthermore, cerebral perfusion was better in the dopamine group than in the control group and thus, results of the evaluation of nervous system function were better in animals treated with dopamine (p < 0.05). Conclusions: Dopamine improved systemic perfusion, cerebral blood supply, and oxygen metabolism after successful resuscitation from VF in a porcine model. All of these factors have profound effects on the cerebral resuscitation.     

Development of an orally infectious Sindbis virus transducing system that efficiently disseminates and expresses green fluorescent protein in Aedes aegypti

We have constructed an orally infectious Sindbis virus, ME2/5'2J/GFP, that expresses green fluorescent protein (GFP) in the midgut of Aedes aegypti and in other tissues as the virus disseminates. This virus has two unique features that are improvements over the SIN-based expression systems currently used in mosquitoes. First, a subgenomic RNA promoter and GFP coding sequence is located 5'- to the second subgenomic promoter and structural genes of the virus. Second, the E2 glycoprotein gene of TE/5'2J/GFP is replaced with the E2 gene of MRE16 SIN virus. The first feature enhances virus genome stability during virus dissemination from the midgut to other tissues and the second allows efficient virus entry into the midgut epithelial cells and then spread of the virus throughout the mosquito.     

Epstein-Barr virus lymphoproliferation after bone marrow transplantation

We review 15 cases of secondary B-cell lymphoproliferative disorders that occurred among 2,475 patients who received allogeneic bone marrow transplants (BMTs) at the Fred Hutchinson Cancer Research Center (Seattle) between 1969 and 1987. The histopathologic findings in 14 of the 15 patients spanned a wide spectrum of lymphoproliferative lesions. One patient had features characteristic of angioimmunoblastic lymphadenopathy. Epstein-Barr virus (EBV) genomic sequences were identified by Southern blot analysis in each of the 13 patients evaluated. Ten of the 12 lesions evaluated originated in donor cells. In two patients, who had mixed chimerism after transplantation, the lesions originated in host cells. The combined evidence from immunoglobulin light chain staining and the analysis of immunoglobulin heavy chain gene rearrangement indicated that the lesions in most patients represented polyclonal proliferations that gave rise to clonal subpopulations. The results indicate an overall actuarial incidence of 0.6% for this complication in BMT recipients. Anti-CD3 monoclonal antibody (MoAb) treatment of acute graft-v-host disease (GVHD) and T cell depletion of the donor marrow were statistically significant risk factors, and GVHD appeared to play a contributing role, particularly in the setting of human leukocyte antigen (HLA) disparity. Two patients had no identifiable risk factors. Prophylaxis or treatment with acyclovir had no detectable effect in the patients; all but two died with uncontrolled lymphoproliferation.     

Diagnostic Accuracy of the Chinese Version of the Trail‐Making Test for Screening Cognitive Impairment

Background/Objectives

The Trail‐Making Test (TMT), which is commonly used to measure executive function, consists of two components (TMT‐A and TMTB). There is a lack of normative TMT data for Chinese elderly adults. This study aimed to evaluate the validity of the TMT in screening for cognitive impairment.

Design

2,294 Chinese‐speaking adults aged 50 to 85: 1,026 with normal cognition (NC), 462 with mild cognitive impairment (MCI), 108 with Alzheimer's disease (AD), 113 with vascular mild cognitive impairment (VaMCI), 121 with vascular dementia (VaD), 282 with uncertain types of dementia, and 15 with mixed dementia. Receiver operating characteristic curve analysis was performed to test the ability of TMT scores to differentiate between NC and cognitive impairment.

Results

Age, education, and sex were significantly associated with TMT completion time. The TMT‐A exhibited sensitivity of 77.8% and specificity of 92.0% with cut‐off value of 98.5 seconds for discriminating AD from NC. The TMT‐B had sensitivity of 83.3% and specificity of 91.8% with a cut‐off value of 188.5 seconds for discriminating AD from NC. The TMT‐A had sensitivity of 85.7% and specificity of 81.6% for discriminating NC from VaD with a cut‐off value of 77.5 seconds, and the TMT‐s had sensitivity of 81.6% and specificity of 83.9% with a cut‐off value of 147.5 seconds. The TMT had less sensitivity distinguishing MCI from NC.

Conclusion

The Chinese version of the TMT is reliable for detecting AD or VaD but poor at distinguishing MCI from NC.     

Chronic graft-versus-host disease in 52 patients: adverse natural course and successful treatment with combination immunosuppression

Fifty-two of 175 (30%) survivors of allogeneic marrow transplantation developed chronic graft-versus-hose diseases (GVHD). Five with limited chronic GVHD had an indolent clinical course with involvement of only the skin and liver. Forty-seven with extensive chronic GVHD had an unfavorable multiorgan disorder that resembled several autoimmune diseases. Thirteen patients with extensive disease (group I) were not treated and only 2 survive with Karnofsky scores >- 70%. Mortality resulted from infections and morbidity from sica syndrome, pulmonary and hepatic insufficiency, scleroderma-like skin disease, and contractures. Another 13 (group II) received a median of 8 mo prednisone and/or a brief course of antithymocyte globulin, and 3 survive without disability. The other 21 (group III) were treated with a combination of prednisone (1.0 mg/kg/q.o.d.) and either cyclophosphamide, procarbazine, or azathioprine (all 1.5 mg/kg/day) for a median of 13 mo. Combination therapy was well tolerated with only modest myelotoxicity. Fifteen in group III had a good and 4 a fair response to treatment while 2 with no response died. Azathioprine and prednisone was the most effective regimen. All therapy has been discontinued in 12 group III patients: GVHD returned in 5 (including 2 who died in spite of retreatment) while 7 remain free of GVHD for a median of 11 (range 6-30) mo observation. Only I group III survivor is disabled and 16 of the original 21 are alive 2-4 yr after transplant with Karnofsky scores of 70%-100%. Thus, combination immmunosuppression appears to favorably affect and, in some cases, premanently arrest the adverse natural course of extensive chronic GVHD.     

The evaluation of gastrointestinal function in diabetic patients

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Incidence and determinants of moderate COPD (GOLD II) in male smokers aged 40–65 years: 5-year follow up

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major health problem with an estimated prevalence of 10-15% among smokers. The incidence of moderate COPD, as defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD), is largely unknown. AIM: To determine the cumulative incidence of moderate COPD (forced expiratory volume in 1 second/forced vital capacity ratio [FEV1/FVC] <0.7 and FEV1 <80% predicted) and its association with patient characteristics in a cohort of male smokers. DESIGN: Prospective cohort study. SETTING: The city of IJsselstein, a small town in the Netherlands. METHOD: Smokers aged 40-65 years who were registered with local GPs, participated in a study to identify undetected COPD. Baseline measurements were taken in 1998 of 399 smokers with normal spirometry (n = 292) or mild COPD (FEV1/FVC <0.7 and FEV1 >or=80% predicted, n = 107) and follow-up measurements were conducted in 2003. RESULTS: After a mean follow-up of 5.2 years, 33 participants developed moderate COPD (GOLD II). This showed an estimated cumulative incidence of 8.3% (95% CI = 5.8 to 11.4) and a mean annual incidence of 1.6%. No participant developed severe airflow obstruction. The risk of developing moderate COPD in smokers with baseline mild COPD (GOLD I) was five times higher than in those with baseline normal spirometry (one in five versus one in 25). CONCLUSIONS: In a cohort of middle-aged male smokers, the estimated cumulative incidence of moderate COPD (GOLD II) over 5 years was relatively high (8.3%). Age, childhood smoking, cough, and one or more GP contacts for lower respiratory tract problems were independently associated with incident moderate COPD.