EOE-13 in the detection of hepatosplenic lymphoma

Thirty-nine patients with lymphoma were evaluated prospectively to determine the usefulness of Ethiodol-Oil-Emulsion-13 (EOE-13) in the detection of hepatosplenic lymphoma by computed tomography. The detection rate in the spleen increased from 8% (before EOE-13 infusion) to 92% (after EOE-13 infusion). In ten of 39 patients (25%) in this series, lymphomatous disease was recognized only on the postinfusion computed tomographic scan. The postinfusion EOE-13 study demonstrated additional visceral abnormalities in 38% of the patients. The potential usefulness, limitations, and toxicity of this hepatosplenic-specific imaging agent are discussed.     

Protein S is a cofactor for activated protein C neutralization of an inhibitor of plasminogen activation released from platelets

Platelets stimulated with thrombin release an inhibitor of plasminogen activator (PAI), which has been shown previously to be neutralized by activated protein C (APC). The requirements for optimal neutralization of PAI activity were investigated. The releasate of gel-filtered human platelets stimulated with thrombin served as a source of PAI. When 6 X 10(8) platelets/mL were incubated with thrombin (1 IU/mL), the releasate contained 18 to 26 ng/mL PAI as determined by incubation of the releasate with urokinase and measurement of residual urokinase activity on plasminogen (S2251). Preincubation of PAI with up to 4 micrograms/mL APC for two hours yielded less than 20% neutralization of PAI activity. In the presence of protein S, phospholipid, and Ca2+, neutralization of PAI activity was time-dependent with 50% neutralization occurring in two hours with 1 microgram/mL APC. The cofactor effects of protein S and phospholipid were concentration- dependent with half-maximal acceleration at approximately 3 micrograms/mL protein S and 10 micrograms/mL phospholipid when the experiments were performed at 1 microgram/mL APC. Diisopropylfluorophosphate-inactivated APC, gla-domainless APC, and thrombin-cleaved protein S had no effect on PAI activity, indicating requirement for preservation of the APC active site and of the Ca2+ binding ability of both APC and protein S. These results suggest coordinate binding of APC and protein S onto phospholipid membrane as a prerequisite for optimal expression of PAI neutralized by APC.     

慢性粒细胞白血病异基因造血干细胞移植34例疗效及生活质量随访

目的：观察异基因造血干细胞移植治疗慢性粒细胞白血病的疗效并进行生活质量评估。 方法：选择2002-03／2007-03在解放军第四军医大学西京医院血液科接受异基因造血干细胞移植18～50岁慢性粒细胞白血病患者34例，其中HLA相合的同胞供者29例，非血缘志愿供者5例。所有患者及其家属对治疗以及研究均知情并签署同意书，医院伦理委员会知情并批准。预处理方案采用改良的马利兰联合环磷酰胺或环磷酰胺联合全身放疗方案。采用标准的环孢素联合短期氨甲喋呤方案预防移植物抗宿主病；无关供者移植加用抗人胸腺细胞球蛋白。所有患者均接受WHOQOL—BREF问卷调查其移植前后的生活质量。 结果：所有患者均获得植入。①移植物抗宿主病出现情况：14.7％（5／34）患者出现急性移植物抗宿主病，41．2％（14，34）患者出现慢性移植物抗宿主病。②移植其他并发症：合并重症肝静脉闭塞病1例；并发纯红细胞性再生障碍性贫血3例，甲状腺功能低下2例，女性雌激素水平低下9例，经积极治疗，大部分获得缓解。③长期生存情况：随访3～60个月，现存活25例（73．5％），其中在慢性期移植者，生存率达82．1％（23／28）。26．4％（9／34）患者在移植后1～50个月时死亡，4例死于白血病复发，5例死于移植并发症。（9生活质量评分：与患者移植前比较，各项指标均有显著的提高（P〈0．05）。 结论：异基因造血干细胞移植是治疗慢性粒细胞白血病的有效方法，尤其在慢性期移植效果较好。移植后长期存活患者的生活质量良好，慢性移植物抗宿主病及女性卵巢功能低下是影响患者生活质量的主要因素。     

Carrier detection in X-linked retinitis pigmentosa

X-linked retinitis pigmentosa (XLRP) is manifested in affected males in their first decade and results in blindness by the third or fourth decade. Carrier detection is difficult since most carrier females show no or only equivocal signs well into or beyond their reproductive years. The genes, or the mutations causing RP have not been identified but at least two have been localised to the short arm of the X chromosome provisionally named RP2 and RP3. Identifying inheritance of one or other of these genes must be done by linkage in families using close, informative DNA markers. Here we report the localisation of a highly informative polymerase chain reaction (PCR) detectable microsatellite marker DXS538 using a previously studied family with X-linked RP3 in which recombination had occurred in the region of importance. The DXS538 dinucleotide repeat locus was previously localised to Xp21.1-p11.21 to study RP3 in one XLRP family. Using published RFLP data we narrowed the localisation of DXS538 to the region Xp21.1 - p11.23. Thus DXS538 is now a convenient diagnostic tool, aiding carrier detection of XLRP in females, as shown in the family presented here.     

Bhutani-based nomograms for the prediction of significant hyperbilirubinaemia using transcutaneous measurements of bilirubin

Aim:  Prospectively establish the relationship between transcutaneous bilirubin (TcB) and total serum bilirubin (TSB), and develop nomograms similar to Bhutani's nomograms, based on our TcB data.
Methods:  Our study sample was from a total population of 1069 infants, near term and term healthy newborns, admitted during 2.5 month period of the study. TSB was performed on all infants who were felt to be clinically jaundiced. Before obtaining the TSB, a TcB was performed (Jaundice Meter Minolta/Draeger JM-103). Measurements were performed on two sites: forehead and mid-sternum, and the mean of both measurements was calculated.
Results:  A total of 1091 paired measurements were obtained from 628 infants. Linear regression showed a significant relation between TSB and TcB (R² of 0.846). In multiple regression analysis, all independent variables studied, i.e. gestational age (or birthweight), age at sampling and ethnicity had a negligible influence on the relationship. We subsequently developed our local-nomograms of hour-specific mean TcB with 40, 75 and 95 percentile lines.
Conclusions:  In our local settings and population, we found a reliable correlation between laboratory measurements of TSB and TcB. We were able to develop our local-Bhutani-based TcB nomograms for screening babies during hospital stay and pre-discharge for assessing the risk of hyperbilirubinaemia.     

Establishment of a schedule of optimal preoperative collection of autologous blood

Autologous blood donation prior to elective surgery can protect patients from unnecessary exposure to allogeneic blood. However, the inappropriate use of autologous blood programs, which results in the collection of excessive quantities of blood or of the collection of any blood prior to low-risk surgical procedures, can be wasteful and potentially hazardous. All patients donating autologous blood at a large institution during a period of three months were studied in an effort to develop a schedule of optimal preoperative collection of autologous blood (SOPCAB), which is similar to a maximum surgical blood order schedule. Some 461 consecutive autologous donations from 264 patients were investigated. For certain surgical procedures, primarily the cardiac and orthopedic procedures, undercollection appeared to be the most common problem. For other procedures (laminectomies, nasal surgery), overcollection was more common. A model is presented for the careful scrutiny of autologous blood collection and use to allow for the creation of a SOPCAB for patients undergoing elective surgery.     

Sickle cell trait is not associated with chronic kidney disease in adult Congolese patients: a clinic-based,cross-sectional study

Chronic kidney disease (CKD) and end-stage renal disease (ESRD) are associated with significant cardiovascular (CV) and renal morbidity and mortality rates, with substantial economic burden.1,2 Therefore, early identification of CKD patients at high risk of progression is urgently needed for early and targeted treatment to improve patient care.1-3 Diabetes and hypertension are the primary risk factors for CKD and ESRD but do not fully account for CKD and ESRD risk.1-3 Marked variability in the incidence of CKD suggests that factors other than diabetes and hypertension contribute to its aetiology.4Family studies have suggested a genetic component to the aetiology of CKD and ESRD.5 In African Americans, high-risk common variants in the Apol1/MYH9 locus may explain up to 70% of the differences in ESRD rates between European and African Americans.5 While this finding has great implications for ESRD, the identification of additional risk factors for CKD, including genetic loci in association with estimated glomerular filtration rate (eGFR), may help to advance our understanding of the underpinnings of CKD in African Americans.5 In this era of identifying genetic risk factors for kidney disease, it may be appropriate to revisit one of the most common genetic disorders: sickle cell haemoglobinopathies.5In this regard, sickle cell trait (SCT), present in approximately 7–9% of African Americans, has been reported to be a potential candidate gene.6 However, conflicting reports exist as to whether SCT is a risk factor for the progression of nephropathy.6,7 Haemoglobin S (HbS) was selected for in Africa because of the protection it affords from malarial infection, a scenario similar to the protection from trypanosomal infection provided by heterozygosity for APOL1 nephropathy risk variants.6Whereas APOL1 contributes to risk for nephropathy in an autosomal recessive inheritance pattern, HbS reportedly had a dominant effect on risk, with SCT being associated with ESRD.6 In line with this finding, a few small studies on African Americans reported HbS as an independent risk factor for CKD and ESRD.8 However, other studies using a large sample of African Americans stated that SCT was not independently associated with susceptibility to ESRD in African Americans,6 highlighting the need for further studies in other populations such as those of sub-Saharan Africa where SCT is prevalent.Although SCT is very prevalent in black Africans,9 few studies have been conducted to assess the association between SCT and CKD.10 In Democratic Republic of Congo (DRC), the prevalence of CKD and SCT has been reported to be 12% and 17–24%, respectively.11-13 No study has evaluated the frequency of SCT among CKD patients to assess its association with reduced kidney function. Therefore, the aim of this clinic-based, cross-sectional study was to assess the potential association between SCT and CKD among adult Congolese patients.     

Effective salvage therapy for lymphoma with cisplatin in combination with high-dose Ara-C and dexamethasone (DHAP)

Ninety patients with progressive recurrent lymphoma were treated with a combination of cisplatin 100 mg/m2 intravenously (IV) by continuous infusion over 24 hours, followed by cytosine arabinoside in two pulses each at a dose of 2 g/m2 given 12 hours apart. Dexamethasone, 40 mg orally or IV, was given on days 1 through 4. Vigorous hydration was reinforced by routine use of mannitol. Treatments were repeated at 3- to 4-week intervals for six to ten courses. Most patients had not achieved complete remission (CR) with prior therapies, which included Adriamycin (all patients) and methotrexate and VP-16 (58 patients). Median patient age was 55 years. Intermediate-grade lymphoma was the most frequent pathologic diagnosis. Seven patients died within two weeks of therapy; of the remaining 83 patients, 28 (34%) or 31% if all patients are considered, achieved CR, and 22 (26.5%) achieved partial remission (PR). Response was evident after the first two cycles of chemotherapy and appeared to be independent of the histopathologic type of lymphoma. To date, only eight of the complete responders have relapsed at a median follow-up of 11 months. The overall 2-year survival in 25%. Further analysis showed that patients with low tumor burden and normal lactic acid dehydrogenase (LDH) had a high CR response rate (67%) and a survival rate of 61% at 2 years. In contrast, patients with both high tumor burden and elevated serum LDH levels had a negligible CR rate, and only 5% are surviving at 1 year. Patients with either high tumor burden with normal LDH or low tumor burden with elevated LDH had an intermediate survival. Myelosuppression-related infection was the most frequent serious complication of this regimen (31%) and the cause of death of ten patients. Acute lysis syndrome was also observed in five patients with high tumor burden and was the cause of death in three of these patients. DHAP has proven to be an effective non-crossresistant regimen for patients with relapsing or refractory lymphoma, particularly for patients who have favorable prognostic characteristics.