The specificity of nephritogenic antibodies. IV. Binding of monoclonal antithymocyte antibodies to rat kidney

Polyclonal rabbit antirat thymocyte serum (ATS) has been shown to form in situ glomerular immune aggregates following perfusion into normal rat kidney ex vivo. This may be due to the presence of T-cell-like epitopes in the rat kidney, or it may be a result of contaminating anti-connective-tissue antibodies in ATS. To exclude the latter possibility we investigated binding to the rat kidney of three different (mouse) monoclonal antirat thymocyte antibodies (anti-T-cell MoAbs), directed to Thy 1.1 antigen, as well as (control) anti-B-cell MoAbs. The MoAbs were incubated in vitro with kidney sections or perfused into the blood-free rat kidney ex vivo. It was shown using immunofluorescence (IF) and immunoelectron microscopy (IEM) (peroxidase technique) that the anti-T-cell MoAbs used, in contrast to anti-B-cell MoAbs, are able to bind with glomerular capillary walls, and with mesangial structures after incubation in vitro or perfusion ex vivo. Although staining patterns are not completely identical, the reaction product is clearly demonstrated throughout the glomerular basement membrane (GBM) and along the plasma membranes of endothelial and epithelial cells, after contact with either of the three anti-T-cell MoAbs used. It is concluded that the presence of T-cell-like epitopes in the rat kidney may lead to immune complex formation following contact with anti-T-cell MoAbs. The nephritogenicity of rabbit ATS, as well as of some batches of clinically used ATS, may also be explained by this mechanism rather than by the usually assumed presence of contaminating antibodies in these polyclonal antisera.     

Femoral capital osteonecrosis: MR finding of diffuse marrow abnormalities without focal lesions

Six painful hips in five patients were examined with magnetic resonance (MR) imaging and were found to have diffuse signal abnormalities in the marrow of the femoral head and neck, which extended into the intertrochanteric area in five cases. The abnormal regions were low in signal intensity on images obtained with a short repetition time (TR) and a short echo time (TE) and were isointense or hyperintense on long TR/TE images--findings that have been attributed by others to bone marrow edema. Edema was also seen in marrow just above the acetabulum in two cases. No focal abnormalities characteristic of osteonecrosis were seen. Osteonecrosis was subsequently shown to be present in all six femoral heads at core biopsy (three cases) or by subsequent development of focal MR abnormalities reported to be highly specific for osteonecrosis (three cases). The affected hips had been radiographically normal or subtly osteopenic and had shown intense radionuclide uptake in the femoral head at scintigraphy, with lesser abnormality in the neck and intertrochanteric region. Follow-up MR examinations of five of the six femoral heads showed the diffuse abnormalities to have been transient. Although diffuse MR abnormalities in the proximal femur are not specific, they may indicate the presence of osteonecrosis of the femoral head.     

Iron, ascorbate and copper status of Sowetan Blacks with calcific chronic pancreatitis

Vitamin C can be used to overcome oxidative stress and ease pain in chronic pancreatitis. But its use is deprecated in conditions of tissue iron overload, because its bioactive form, ascorbate, can accelerate free-radical reactions that are driven by transition metals. We measured iron, ascorbate and copper in Sowetan Blacks (RSA) with chronic pancreatitis, obtaining serum/plasma from 14 consecutive patients and 15 controls. Compared with data from corresponding groups in Manchester, African samples had less ascorbate (p < 0.0001), but more caeruloplasmin (p < 0.0001). African and British controls had comparable iron and iron-binding capacity. Plasma from African patients had less ascorbate than that from African controls (p < 0.005) and in six samples, ferritin exceeded 300 micrograms/l (677 pmol/l). Low- molecular-mass iron or copper, capable of participating in free radical reactions, was not detected. British patients, had similar caeruloplasmin levels to African patients but higher ascorbate levels. There is no evidence of iron overload in our African samples. Outwardly healthy controls from Soweto have elevated levels of caeruloplasmin, possibly to compensate for dietary deficiency of ascorbate. Persistent oxidative stress is a unifying feature of chronic pancreatitis, but its degree is higher in African than British patients. Supplements of vitamin C should be safe in Blacks of southern Africa.      

Biomechanical analysis of tendon transfers for massive rotator cuff tears

OBJECTIVE: To determine why certain tendon transfers are mechanically more effective than other tendon transfers for the treatment of a massive rotator cuff tear. DESIGN: A tendon transfer procedure of latissimus dorsi, teres major or a combination of these two to the insertions of either teres minor, infraspinatus, supraspinatus, or subscapularis is simulated using a biomechanical musculoskeletal model of the upper extremity. BACKGROUND: Massive rotator cuff tears are not easily repaired. To compensate for the loss of rotator cuff function, techniques such as muscle transfers are developed. METHODS: Three range of motion tasks were used as input to the Delft shoulder and elbow model. The muscle parameters of the Delft shoulder and elbow model were modified to simulate a rotator cuff tear. A biomechanical analysis of the transferred muscles was performed, taking outcome variables such as moment arms, muscle length and muscle force into account. RESULTS: Due to the massive rotator cuff tear, an elevation and external rotation moment is lost. When the tendon was transferred to the insertions of infraspinatus or supraspinatus, the humerus was capable of elevating and externally rotating. CONCLUSIONS: On the basis of mechanical parameters such as moment arms, muscle length and force it can be concluded that a tendon transfer of the teres major to the supraspinatus insertion will produce the best functional outcome in the treatment of massive rotator cuff tears. RELEVANCE: To find biomechanical evidence for an optimal tendon transfer that will lead to improved treatment of patients with a massive rotator cuff tear.     

自体造血干细胞的体外净化

目的:综合分析自体造血干细胞体外净化的方法。资料来源:应用计算机检索Medline 1991-01/2003-12有关自体造血干细胞体外净化方法的文章,检索词“purging,HSCT”,并限定文章语言种类为English。同时计算机检索CNKI数据库1991-01/2003-12有关自体造血干细胞体外净化方法的文章,检索词“体外净化,PUVA”,并限定文章语言种类为中文。资料选择:对相关资料进行整理,选取同一领域、不同方面的文献,以近期发表或权威杂志的文章优先。资料提炼:共检索到42篇有关自体造血干细胞体外净化方法的文献,其中24篇文章符合要求。排除18篇,其中15篇系重复同一研究,3篇为Meta分析。资料综合:自体造血干细胞的体外净化方法很多,如物理方法、生物学方法、药物方法、免疫净化、基因净化等。每种净化方法都有其各自的优势和不足,如淋巴系统疾病可以采用免疫净化;慢性粒细胞白血病患者可考虑反义技术;大多数患者则均可以考虑药物净化的方法。结论:针对不同的疾病,可以选择不同的净化方法,还可以将几种净化方法联合起来,其效果和方法的改进也在不断的研究探索中。     

Reduction in transmission of hepatitis C after the introduction of a heat-treatment step in the production of C1-inhibitor concentrate

BACKGROUND: The transmission of viral infections via protein concentrates made from a large pool of plasma depends on the selection of donors, fractionation process, and virucidal methods. To date, no data are available on the infectivity risk of plasma concentrates of the inhibitor of the first component of complement (C1-INH). STUDY DESIGN AND METHODS: The prevalence of blood-borne viral infections and levels of transaminases were evaluated in patients treated with a large- pool plasma concentrate of the inhibitor of C1-INH before and after the introduction of virucidal methods. The study included 85 patients with hereditary angioedema and 4 with acquired angioedema. The patients were divided into three groups: 1) 48 untreated patients; 2) 22 patients treated with non-virus-inactivated C1-INH concentrates; and 3) 19 patients treated with virus-inactivated concentrates. Serum samples obtained at various times after the infusion of concentrate were assayed for alanine amino-transferase and tested for hepatitis B surface antigen and antibodies to hepatitis C virus (anti-HCV) and human immunodeficiency virus (anti-HIV); anti-HCV-negative subjects exposed to the concentrate were also tested for HCV RNA. RESULTS: Prevalences of HCV infection and elevated alanine aminotransferase are significantly lower in patients treated with virus-inactivated concentrates than in those exposed to non-virus-inactivated concentrates. No patients were anti-HIV positive. CONCLUSION: This study suggests that C1-INH concentrates transmitted HCV, but that the virucidal methods adopted are effective in reducing the infectivity.     

Serial immunoreactive erythropoietin levels in autologous blood donors

The variations in plasma erythropoietin (EPO) concentration during preoperative deposit of autologous blood were studied in 12 patients (8 men, 4 women). Four donations were scheduled at weekly intervals. A predonation hemoglobin concentration of 11 g per dL (110 g/L) was required. Hemoglobin concentration decreased from 14.3 +/- 1.1 g per dL (143 +/- 11 g/L) (mean +/- SD) before the first donation to 11.7 +/- 0.7 g per dL (117 +/- 7 g/L) on Day 22 (p less than or equal to 0.0001). Reticulocyte counts increased from a median of 31,800 (range, 4900-95,000) per microL (median, 32 x 10(9)/L [range, 5-95 x 10(9)/L]) to 93,800 (16,800-194,900) per microL (median, 94 x 10(9)/L [range, 17-195 x 10(9)/L]) on Day 28 (p less than or equal to 0.01). Plasma EPO concentration was 17.8 +/- 5.1 mU per mL prior to the first donation and displayed a small and transient peak after each donation. A sustained elevation followed each peak. Although plasma EPO concentration differed significantly from the baseline value after the first donation, only the peak concentrations after the second (35.5 +/- 15.5 mU/mL), third (38.0 +/- 14.5 mU/mL), and fourth (36.1 +/- 11.0 mU/mL) donations exceeded the normal range. The moderate, biphasic increase in plasma EPO concentration and the moderate increase in erythropoiesis suggest two strategies in autologous blood donation that should be investigated with respect to efficiency and safety: 1) more aggressive donation schemes, which reduce donation intervals and/or the minimum hemoglobin concentration and 2) the administration of recombinant human EPO.     

Transmission of hepatitis G virus in patients with angioedema treated with steam-heated plasma concentrates of C1 inhibitor

BACKGROUND: Hepatitis G virus (HGV) is a blood-borne flavivirus that may cause acute and chronic transfusion-transmitted infections. Patients with complement component 1 (C1) inhibitor (C1-INH) deficiency may acquire blood-borne infections through infusion of plasma concentrates. STUDY DESIGN AND METHODS: Serum samples from 84 patients with C1-INH deficiency (19 who received unmodified C1-INH concentrates, 23 who received steam-heated concentrates, and 42 untreated patients) were tested for HGV RNA and hepatitis C virus (HCV) RNA by a nested polymerase chain reaction (PCR). The samples were also tested for antibodies to the E2 envelope protein of HGV (anti-HGV) and to HCV with enzyme-linked immunosorbent assays. RESULTS: Nine (11%) patients had serum HGV RNA; that is, 7 (17%) of 42 patients previously treated with C1-INH concentrates and 2 of 42 previously untreated patients. HGV RNA was as common in the 19 patients treated with unmodified concentrates as in the 23 given steam-heated concentrates (16 vs. 17%, p = 0.60). Anti-HGV was more common among the recipients of unmodified concentrates than among those given steam-heated concentrates (26 vs. 0%, p = 0.014). HCV RNA was more frequently detected in treated patients than in untreated patients (33 vs. 7%, p = 0.005) and in the 19 recipients of unmodified concentrates than in the 23 treated with steam-heated concentrates (58 vs. 16%, p = 0.003). Only one HGV RNA- seropositive patient had elevated serum aminotransferase activity, compared to 11 with HCV RNA. CONCLUSION: HGV was transmitted by both unmodified and steam-heated concentrates, but it caused persistent viremia in a minority of the cases and was rarely associated with liver disease.     

Adverse reactions in blood donors with a history of seizures or epilepsy

BACKGROUND: Individuals with epilepsy or seizure disorders are restricted from donating blood because of concern that they are prone to adverse donor reactions such as syncope and convulsions. A study evaluating whether that concern is warranted is reported. STUDY DESIGN AND METHODS: During a 2-year period beginning in 1987, blood donors in Maryland with a history of seizures were actively recruited by the American Red Cross. Adverse donor reactions were classified as "slight", indicating dizziness and nausea without loss of consciousness; "moderate," denoting syncope; and "severe," indicating convulsive syncope. RESULTS: There were 329,143 satisfactory blood donations; 613 individuals reporting a history of seizures donated blood a total of 723 times. Among donors with seizures, 186 (35.7%) were taking antiepileptic medication, and 61 (8.4%) had had one or more seizures in the preceding year. Individuals with seizures had a low incidence of adverse reactions (3.34%). Although this incidence was slightly higher than that in the entire population (2.24%), the difference was not significant. In particular, the risk of syncope with or without convulsive activity was low for people with seizures (0.21%) and not significantly greater than that in other donors (0.28%). CONCLUSION: Individuals with seizures or epilepsy are not at greater risk for adverse reactions after blood donation, and major restrictions on their participation as blood donors are not warranted.