Reduction in baroreflex cardiovascular responses due to venous infusion in the rabbit.
We studied reflex bradycardia and depression of mean arterial blood pressure (MAP) during left aortic nerve (LAN) stimulation before and after volume infusion in the anesthetized rabbit. Step increases in mean right atrial pressure (MRAP) to 10 mm Hg did not result in a significant change in heart rate or MAP. After volume loading, responses to LAN stimulation were not as great and the degree of attenuation was propoetional to the level of increased MRAP. A change in responsiveness was observed after elevation of MRAP by only 1 mm Hg, corresponding to less than a 10% increase in average calculated blood volume. after an increase in MRAP of 10 mm Hg, peak responses were attenuated by 44% (heart rate) and 52% (MAP), and the initial slopes (rate of change) were reduced by 46% (heart rate) and 66% (MAP). Comparison of the responses after infusion with blood and dextran solutions indicated that hemodilution was an unlikely explanation for the attenuation of the reflex responses. Total arterial baroreceptor denervation (ABD) abolished the volume-related attenuation was still present following bilateral aortic nerve section or vagotomy. It thus appears that the carotid sinus responds to changes inblood volume and influences the reflex cardiovascular responses to afferent stimulation of the LAN. On the other hand, cardiopulmonary receptors subserved by vagal afferents do not appear to be involved. (+info)
A prospective study on TT virus infection in transfusion-dependent patients with beta-thalassemia.
A novel DNA virus designated TT virus (TTV) has been reported to be involved in the development of posttransfusion non-A-C hepatitis. We evaluated the frequency and natural course of TTV infection in a cohort of transfusion-dependent thalassemic patients in a 3-year follow-up study. Ninety-three serum hepatitis C virus (HCV) antibody-negative patients (median age of 8 years; range, 0 to 25) from eight centers were studied. Of them, 34 (37%) had an abnormal alanine-aminotransferase (ALT) baseline pattern, and the other 12 (13%) showed ALT flare-ups during the follow-up. TTV DNA in patient sera collected at the time of enrollment and at the end of follow-up was determined by polymerase chain reaction (PCR). In parallel, serum samples from 100 healthy blood donors were also tested. At baseline, 87 patient sera (93.5%) tested positive for the TTV DNA. Of these TTV DNA-positive patients, 84 (96.5%) remained viremic at the end of the study period. Of the 6 TTV DNA-negative patients, 3 acquired TTV infection during follow-up. However, no definite relation was observed between the results of TTV DNA determination and ALT patterns. TTV viremia was also detectable in 22% of blood donors. In conclusion, TTV infection is frequent and persistent among Italian transfusion-dependent patients. The high rate of viremia observed in healthy donors indicates that the parenteral route is not the only mode of TTV spread. (+info)
Soluble HLA class I, HLA class II, and Fas ligand in blood components: a possible key to explain the immunomodulatory effects of allogeneic blood transfusions.
The immunomodulatory effect of allogeneic blood transfusions (ABT) has been known for many years. However, a complete understanding of the effects of ABT on the recipient's immune system has remained elusive. Soluble HLA class I (sHLA-I), HLA class II (sHLA-II), and Fas ligand (sFasL) molecules may play immunoregulatory roles. We determined by double-determinant immunoenzymatic assay (DDIA) sHLA-I, sHLA-II, and sFasL concentrations in different blood components. sHLA-I and sFasL levels in red blood cells (RBCs) stored for up to 30 days and in random-donor platelets are significantly (P <.001) higher than in other blood components and their amount is proportionate to the number of residual donor leukocytes and to the length of storage. Blood components with high sHLA-I and sFasL levels play immunoregulatory roles in vitro as in allogeneic mixed lymphocyte responses (MLR) and antigen-specific cytotoxic T-cell (CTL) activity, and induce apoptosis in Fas-positive cells. These data suggest that soluble molecules in blood components are functional. If these results are paralleled in vivo, they should be taken into account in transfusion practice. Blood components that can cause immunosuppression should be chosen to induce transplantation tolerance, whereas blood components that lack immunosuppressive effects should be preferred to reduce the risk of postoperative complications and cancer recurrence. (+info)
Structural and functional consequences of antigenic modulation of red blood cells with methoxypoly(ethylene glycol).
We previously showed that the covalent modification of the red blood cell (RBC) surface with methoxypoly(ethylene glycol) [mPEG; MW approximately 5 kD] could significantly attenuate the immunologic recognition of surface antigens. However, to make these antigenically silent RBC a clinically viable option, the mPEG-modified RBC must maintain normal cellular structure and functions. To this end, mPEG-derivatization was found to have no significant detrimental effects on RBC structure or function at concentrations that effectively blocked antigenic recognition of a variety of RBC antigens. Importantly, RBC lysis, morphology, and hemoglobin oxidation state were unaffected by mPEG-modification. Furthermore, as shown by functional studies of Band 3, a major site of modification, PEG-binding does not affect protein function, as evidenced by normal SO4- flux. Similarly, Na+ and K+ homeostasis were unaffected. The functional aspects of the mPEG-modified RBC were also maintained, as evidenced by normal oxygen binding and cellular deformability. Perhaps most importantly, mPEG-derivatized mouse RBC showed normal in vivo survival ( approximately 50 days) with no sensitization after repeated transfusions. These data further support the hypothesis that the covalent attachment of nonimmunogenic materials (eg, mPEG) to intact RBC may have significant application in transfusion medicine, especially for the chronically transfused and/or allosensitized patient. (+info)
Endoscopic retreatment compared with surgery in patients with recurrent bleeding after initial endoscopic control of bleeding ulcers.
BACKGROUND AND METHODS: After endoscopic treatment to control bleeding of peptic ulcers, bleeding recurs in 15 to 20 percent of patients. In a prospective, randomized study, we compared endoscopic retreatment with surgery after initial endoscopy. Over a 40-month period, 1169 of 3473 adults who were admitted to our hospital with bleeding peptic ulcers underwent endoscopy to reestablish hemostasis. Of 100 patients with recurrent bleeding, 7 patients with cancer and 1 patient with cardiac arrest were excluded from the study; 48 patients were randomly assigned to undergo immediate endoscopic retreatment and 44 were assigned to undergo surgery. The type of operation used was left to the surgeon. Bleeding was considered to have recurred in the event of any one of the following: vomiting of fresh blood, hypotension and melena, or a requirement for more than four units of blood in the 72-hour period after endoscopic treatment. RESULTS: Of the 48 patients who were assigned to endoscopic retreatment, 35 had long-term control of bleeding. Thirteen underwent salvage surgery, 11 because retreatment failed and 2 because of perforations resulting from thermocoagulation. Five patients in the endoscopy group died within 30 days, as compared with eight patients in the surgery group (P=0.37). Seven patients in the endoscopy group (including 6 who underwent salvage surgery) had complications, as compared with 16 in the surgery group (P=0.03). The duration of hospitalization, the need for hospitalization in the intensive care unit and the resultant duration of that stay, and the number of blood transfusions were similar in the two groups. In multivariate analysis, hypotension at randomization (P=0.01) and an ulcer size of at least 2 cm (P=0.03) were independent factors predictive of the failure of endoscopic retreatment. CONCLUSIONS: In patients with peptic ulcers and recurrent bleeding after initial endoscopic control of bleeding, endoscopic retreatment reduces the need for surgery without increasing the risk of death and is associated with fewer complications than is surgery. (+info)
Primary percutaneous transluminal coronary angioplasty performed for acute myocardial infarction in a patient with idiopathic thrombocytopenic purpura.
A 72-year-old female with idiopathic thrombocytopenic purpura (ITP) complained of severe chest pain. Electrocardiography showed ST-segment depression and negative T wave in I, aVL and V4-6. Following a diagnosis of acute myocardial infarction (AMI), urgent coronary angiography revealed 99% organic stenosis with delayed flow in the proximal segment and 50% in the middle segment of the left anterior descending artery (LAD). Subsequently, percutaneous transluminal coronary angioplasty (PTCA) for the stenosis in the proximal LAD was performed. In the coronary care unit, her blood pressure dropped. Hematomas around the puncture sites were observed and the platelet count was 28,000/mm3. After transfusion, electrocardiography revealed ST-segment elevation in I, aVL and V1-6. Urgent recatheterization disclosed total occlusion in the middle segment of the LAD. Subsequently, PTCA was performed successfully. Then, intravenous immunoglobulin increased the platelet count and the bleeding tendency disappeared. A case of AMI with ITP is rare. The present case suggests that primary PTCA can be a useful therapeutic strategy, but careful attention must be paid to hemostasis and to managing the platelet count. (+info)
Hormonal changes in thalassaemia major.
Patients with severe thalassaemia major suffer endocrine and other abnormalities before their eventual death from iron overload due to repeated blood transfusions. The endocrine status of 31 thalassaemic patients aged 2-5 to 23 years was investigated. Exact data were available on the rate and duration of blood transfusion in all of them and in many the liver iron concentration was also known. Although the patients were euthyroid, the mean serum thyroxine level was significantly lower, and the mean thyrotrophic hormone level significantly higher, compared with the values found in normal children. Forty oral glucose tolerance tests with simultaneous insulin levels were performed in 19 children, of whom 5 developed symptomatic diabetes and one had impaired tolerance. Previous tests on all 6 patients were available and some showed raised insulin levels possibly due to insulin resistance. 2 patients had clinical hypoparathyroidism and are described. The parathyroid hormone levels determined by radioimmunoassay in 25 patients were below the mean for the age group in all and outside the reference range in 16. Nonfasting plasma calcium levels were not reduced. Puberty was delayed in some patients. Concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) measured in urine from 7 girls and 5 boys showed considerable variation. In the boys there was an overall tendency for FSH and LH excretion to be low with regard to age, but with respect to puberty rating FSH exretions were normal or low and LH normal or raised. The girls showed a tendency for LH but not FSH excretion to be raised in relation to puberty rating. The severity of the endocrine changes was related to the degree of iron loading and is discussed in relation to previous work in which the iron loading has rarely been accurately indicated nor parathyroid status assessed. (+info)
Prospective randomized multicenter study comparing cyclosporin alone versus the combination of antithymocyte globulin and cyclosporin for treatment of patients with nonsevere aplastic anemia: a report from the European Blood and Marrow Transplant (EBMT) Severe Aplastic Anaemia Working Party.
We report the results of the first prospective randomized multicenter study of immunosuppressive treatment in patients with previously untreated nonsevere aplastic anemia (AA) as defined by a neutrophil count of at least 0.5 x 10(9)/L and transfusion dependence. Patients were randomized to receive cyclosporin (CSA) alone or the combination of horse antithymocyte globulin ([ATG] Lymphoglobuline; Merieux, Lyon, France) and CSA. The endpoint of the study was the hematologic response at 6 months. One hundred fifteen patients were randomized and assessable with a median follow-up period of 36 months; 61 received CSA and 54 ATG and CSA. In the CSA group, the percentage of complete and partial responders was 23% and 23%, respectively, for an overall response rate of 46%. A significantly higher overall response rate of 74% was found in the ATG and CSA group, with 57% complete and 17% partial responders (P =. 02). Compared with CSA alone, the combination of ATG and CSA resulted in a significantly higher median hemoglobin level and platelet count at 6 months. Fewer patients required a second course of treatment before 6 months due to a nonresponse. In the CSA group, 15 of 61 (25%) patients required a course of ATG before 6 months because of disease progression, compared with only 3 of 54 (6%) in the ATG and CSA group. The survival probabilities for the two groups were comparable, 93% (CSA group) and 91% (ATG and CSA group), but at 180 days, the prevalence of patients surviving free of transfusions, which excluded patients requiring second treatment because of nonresponse, death, disease progression, or relapse, was 67% in the CSA group and 90% in the ATG and CSA group (P =.001). We conclude that the combination of ATG and CSA is superior to CSA alone in terms of the hematologic response, the quality of response, and early mortality, and a second course of immunosuppression is less frequently required. (+info)