Autologous stem cell‐based therapy for sickle cell leg ulcer: a pilot study

Recurrent chronic leg ulcers are among the most severe vasculopathic complications of sickle cell disease (SCD). Their treatment remains a challenge. Stem cell therapy with bone marrow mononuclear cells (BMMC) is a promising new therapeutic option for other forms of chronic ulcers. This prospective pilot study was performed to evaluate safety and feasibility of BMMC implantation in patients with SCD and chronic leg ulcers (SCLU). Ulcer closure, recurrence and local pain were evaluated. BMMC were successfully administered to 23 SCLU patients and no serious adverse events occurred. During the 6‐month follow‐up period, 91·3% of patients had improved ulcer pain compared with baseline and 29·2% of the treated ulcers achieved total healing. The frequency of progenitor stem cells (CD34CD45^low and fibroblast colony‐forming units) in BMMC was found to be significantly reduced in SCLU patients and compared to SCD patients without ulcers (P < 0·004 and P < 0·01, respectively). No relationship was observed between treatment outcome and the number of implanted BM progenitor stem cells. In conclusion, BMMC implantation is a feasible and safe procedure, showing favourable outcomes for the treatment of SCLU, and encouraging further controlled clinical trials.     

Accuracy of dual-energy radiographic absorptiometry of the lumbar spine: cadaver study

Dual-energy radiographic absorptiometry (DRA) was used to measure the bone mineral content and area density of lumbar vertebrae (L2-L3) in 11 cadavers. These data were subsequently compared with measured ash content and density. Excellent correlation was obtained between bone mineral content measured with DRA and ash weight (r = .963, P less than .0001). The accuracy error in determining mineral content in lumbar vertebrae with DRA was about 9%. In addition, strong correlation was observed between bone mineral density measured with DRA and ash density (r = .881, P less than .0001).     

Neutral glycosphingolipid expression in B-cell neoplasms

The expression of neutral glycosphingolipids (GSL) in 37 B-cell neoplasms [7 acute lymphocytic leukemia (ALL), 5 Burkitt's lymphoma (BL), 7 chronic lymphocytic leukemia (CLL), 5 diffuse, poorly differentiated lymphoma (DPDL), 6 diffuse histiocytic lymphoma (DHL), 3 hairy-cell leukemia (HCL), and 4 multiple myeloma (MM)] was examined. Patterns of expression of simple (GlcCer, LacCer) and globo-series GSL (Gb3, Gb4) were found for each tumor type. In addition, pre-B ALL expressed the neo-lacto series GSL, paragloboside, which was not significantly seen at later stages of maturation. As a group, leukemias expressed about 10 times higher ratios of simple GSL to Globo-series GSL as compared to lymphomas, regardless of stage of differentiation. Significant amounts of GSL of other series were not found except in one CLL which contained asialo-GM2. GSL phenotype in these cells was not grossly affected by cell genotype since pre-B ALL containing Philadelphia chromosome t(9q;22q) translocations were similar to other ALL; and DHL with t(8q;14q) translocations had GSL patterns similar to other DHL samples and dissimilar to GSL patterns found in Burkitt's lymphomas with t(8q;14q). Differences in GSL expression among the different types of B-cell neoplasm suggested that GSL patterns form a phenotypic map that may complement the traditional glycoprotein immunophenotypic map and contribute to our understanding of the biology of these diseases and B-cell differentiation.     

Isoleucine metabolism by leukemic and normal human leukocytes in relation to cell maturity and type

The metabolism of an essential amino acid, isoleucine, by human leukemic and gradient-separated normal human leukocytes of various types and maturity was studied. Blood leukocytes were isolated and incubated with (U-14C) isoleucine. Separation of metabolic intermediates was accomplished by sequential extraction. The rate of isoleucine incorporation into protein by immature cells from untreated patients with acute leukemia (15.9 plus or minus 2.4 nmoles/hr per 10-8 leukocytes) was considerably higher than the rates of incorporation by mature neutrophils (3.2 plus or minus 0.5 nmoles/hr per 10-8 leukocytes), lymphocytes (7.7 plus or minus 1.2 nmoles/hr per 10-8 leukocytes), and eosinophils (6.2 plus or minus 1.3 nmoles/hr per 10-8 leukocytes). Those cell preparations with more blast cells had higher rates of protein synthesis. In addition, those cells with greater thymidine incorporation had higher rates of protein synthesis. The leukocytes both oxidized isoleucine and incorporated it into cell isoleucine and incorporated it into cell lipid. The rates of these metabolic processes were characteristic for various types and maturity of leukocytes. This study demonstrates a relationship of rate of protein synthesis to leukocyte immaturity. This relationship is maintained in neoplastic leukocytes. It suggests that the requirement of the mitotic process for newly synthesized protein is greater than that for the elaboration of the protein products of the mature leukocyte.     

Surgical Treatment and Clinical Outcome of GH-Secreting Adenomas in Elderly Patients

Summary. Patients older than 65 years represent 3–5% of all acromegalic patients. The old age of the patients and the higher incidence of cardiovascular and metabolic complications related to acromegaly could increase the intra- and peri-operative risk, so that medical treatment is usually recommended as a therapy of choice. The aim of this retrospective study was to investigate the impact of transsphenoidal surgery in a series of 22 elderly patients with active acromegaly, with special regard to anaesthesiological risk, peri-operative complications, and clinical outcome. Despite an increased anesthesiological risk being present in 16/22 patients, no complication occurred during surgery. Similarly, no post-operative mortality or major complications were observed. Biochemical cure, defined at 6 months by glucose-suppressed plasma GH levels below 1 ng/ml and normal age-corrected IGF-I value levels, was achieved in 68% of patients and no recurrence of disease was observed in the subsequent follow-up (mean 5.2±2.1 years). A significant cardiovascular improvement was observed in cured patients, with a decrease of left ventricular mass index (91.3±20.1 vs 115.9±15.0 g/m²; P<0.005), as measured by echocardiography, as well as a slight but significant decrease of systolic and diastolic blood pressure values (130.0±12.1 mmHg vs 137.6±13.5 mmHg P<0.05; and 84.2±6.4 mmHg vs 88.8±7.5 mmHg P<0.05, respectively). A significant post-operative improvement of glucose tolerance was also observed in this group. We conclude that transsphenoidal surgery, if well planned and carefully performed, is safe and able to induce a significant cardiovascular and metabolic improvement even in elderly acromegalic patients.     

Atypical tentorial meningioma 30 years after radiotherapy for a pituitary adenoma

Although the human central nervous system used to be considered relatively resistant to the carcinogenic action of ionizing radiation, several lines of evidence now document a high incidence of secondary tumors in irradiated patients. The numerous reports of radiation-induced cerebral meningiomas generally distinguish those induced by high-dose radiation from those induced by low-dose radiation. We describe the case of patient who underwent subtotal resection of a chromophobe pituitary adenoma at the age of 18 years, who was successively treated by conventional fractionated radiotherapy with gamma rays emitted by a source of ⁶⁰Co until a total dose of 41 Gy. Over the next 30 years the patient experienced all the known late effects of radiation, including panhypopituitarism, cranial-nerve deficits (II, III and VI), massive radiation necrosis involving the left cerebral hemisphere and causing right hemiparesis and aphasia and, ultimately, an atypical tentorial meningioma with early recurrence after total resection. Received: 13 December 2000 / Accepted in revised form: 19 November 2001     

Inhibition of cell proliferation with an HLA-A-specific monoclonal antibody

A new mouse IgG2A monoclonal antibody--JD 12--is described, which was selected for its ability to inhibit peripheral blood mononuclear cell (PBMC) proliferation. Serologic, immunoprecipitation and immunoelectrophoretic studies showed JD12 to be monomorphically reactive with HLA-A molecules with an affinity of 10(9) M-1. JD12 was capable of inhibiting growth in resting or stimulated PBMC with an ID50 of 300 ng/ml in a time-dependent and dose-dependent manner without cytotoxicity. IgG, F(ab)2 and F(ab) were active. Growth stimulation by phorbol ester was not inhibited, suggesting that JD12 action occurred prior to protein kinase C activation. DNA and RNA synthesis were both slowed with a resulting G0/G1 block. Analysis of separated PBMC components showed that adherent cells displayed increased activity (clumping and RNA synthesis) upon JD12 binding. In addition, the inhibitory activity of JD12 could be transferred to new cultures by cell-free, IgG-free supernatant from JD12-treated PBMC, suggesting that the antiproliferative effects could be mediated, at least in part, in an indirect manner through an inhibitory factor. Therefore, potent, noncytotoxic inhibition of cell proliferation, DNA and RNA synthesis via MHC molecules can be mediated specifically through effects initiated by binding to HLA-A molecules alone.     

Safety trial with the 5HT1B/1D agonist avitriptan (BMS-180048) in patients with migraine who have experienced pressure, tightness, and/or pain in the chest, neck, and/or throat following sumatriptan

We investigate whether symptoms of pressure, tightness, and/or pain in the chest, neck, and/or throat after administration of the 5HT_1B/1D agonist avitriptan were associated with objective impairment of the myocardial function on 12-lead electrocardiogram (ECG), continuous ECG (Holter) monitoring, and echocardiography. Migraine sufferers who in two-thirds of alt attacks treated with sumatriptan had experienced chest/throat/neck symptoms were chosen for study. Baseline measures included vital signs, a 12-lead ECG and an echocardiogram. Patients ( n =51) who had no clinically significant abnormality at baseline received a high dose (150 mg) of avitriptan orally outside of a migraine attack. If pressure, tightness, and/or pain in the chest, neck, and/or throat occurred, an ECG was obtained, and a repeat echocardiogram was done while the symptoms were present in order to monitor for impairment of myocardial function. If symptoms of these types did not occur within 60 min after administration of the study drug, a second echocardiogram was obtained. Forty-five patients (88%) reported at least one adverse event and 23 (45%) experienced pressure, tightness, and/or pain in the chest, neck, and/or throat after administration of avitriptan. No clinically significant myocardial abnormalities were observed in any patient, even in those who had experienced the targeted symptoms. No other serious adverse event occurred. We concluded that the typical 5HT_1B/1D agonist-induced chest/throat/neck symptoms are most unlikely to be of cardiovascular origin.     

Efficacy of confrontational counselling for smoking cessation in smokers with previously undiagnosed mild to moderate airflow limitation: study protocol of a randomized controlled trial

Background  

The use of spirometry for early detection of chronic obstructive pulmonary disease (COPD) is still an issue of debate, particularly because of a lack of convincing evidence that spirometry has an added positive effect on smoking cessation. We hypothesise that early detection of COPD and confrontation with spirometry for smoking cessation may be effective when applying an approach we have termed "confrontational counselling"; a patient-centred approach which involves specific communication skills and elements of cognitive therapy. An important aspect is to confront the smoker with his/her airflow limitation during the counselling sessions. The primary objective of this study is to test the efficacy of confrontational counselling in comparison to regular health education and promotion for smoking cessation delivered by specialized respiratory nurses in current smokers with previously undiagnosed mild to moderate airflow limitation.     

女性护理专业学生心理健康相关因素分析

目的:分析护理专业学生心理健康的影响因素。方法:于2005-12-01/15按整群抽样法抽取西安市高校在读的护理专业学生515名作为被调查对象。症状自评量表总分≥187为高分组,总分≤116为低分组。高分组与低分组配比的条件是均为女性,年龄相差不超过3岁。采用症状自评量表、简易应对方式问卷、自尊量表、护理专业学生相关状况调查表进行问卷调查。对调查变量进行单因素和多因素Logistic回归分析。结果:共发放问卷515份,其中2名学生生病未填写调查表,应答率为99.6%。调查中有效问卷共507份,有效率为98.8%。症状自评量表总分高分组与低分组学生各100名。①护理专业学生心理健康相关个人因素(计量变量)单因素分析结果:高分组积极应对、自尊水平得分明显低于低分组(20.47±5.02,22.15±6.02;25.91±3.60,30.96±3.25),差异有显著性意义(P<0.05,P<0.01)。高分组消极应对得分明显高于低分组(12.57±4.08,8.00±4.12),差异有显著性意义(P<0.01)。②护理专业学生心理健康相关个人因素(二分类变量)单因素分析结果表明,高分组与低分组比较差异有显著性的因素有独生子女、远离家人、孤独、学习压力大、担心拿不到学位、自我实现需要的满足、经常被人误会、受人歧视、失恋、有知心朋友、无处倾诉苦恼、睡眠型态紊乱、近1年来本人健康改变、适应新环境、经常参加体育活动、担心毕业分配、现有最担心的事情。③多因素分析显示,学习压力大(OR=10.017)、近1年来本人健康改变(OR=4.384)为护理专业学生心理健康状况不良的独立危险因素,而自我实现需要的满足(OR=0.037)、高水平自尊(OR=0.357)是保护因素。结论:护理专业学生心理健康状况与教育、成长、社会环境等多方面因素相关,其心理健康干预需考虑学生的个人因素有针对性地进行。