Effect of saralasin upon plasma catecholamines in hypertensive patients

The effect of saralasin, a clinically employed angiotensin antagonist, upon hemodynamics and plasma catecholamine concentration was compared to the infusion of noradrenaline. These studies were carried out to determine if a transient pressor effect frequently observed during saralasin infusion might be mediated by release of catecholamines from the adrenal medulla. After five minutes of saralasin infusion, mean arterial pressure rose significantly, pulse rate fell slightly, and plasma noradrenaline increased by 115 +/- 28 pg./ml. Plasma adrenaline was unchanged. After 30 minutes of saralasin infusion, mean arterial pressure was at control levels and plasma catecholamine concentrations were also no different from pre-infusion levels. Infusion of noradrenaline produced a hemodynamic pattern similar to that observed during the first five minutes of saralasin infusion. However, there was a thirteen-fold increase of plasma noradrenaline observed when compared to the first five minutes of saralasin infusion. It was concluded that the transient pressor action of saralasin could not be explained by release of catecholamines from the adrenal medulla. However, the very slight increase in plasma norepinephrine observed during the first five minutes of saralasin infusion may imply altered function of sympathetic neurons.     

Adiponectin concentrations are influenced by renal function and diabetes duration in Pima Indians with type 2 diabetes

Adiponectin is produced exclusively by adipocytes, and its serum concentration is inversely associated with adiposity. This study examines the relationship among diabetes, renal function, and serum adiponectin in Pima Indians. Serum adiponectin was measured in 1069 people in whom glycemia and renal function had been measured. Serum adiponectin, adjusted for age, sex, and body mass index, was lowest in those with impaired glucose regulation or diabetes of less than 10 yr duration and highest in those with normal glucose tolerance or diabetes of duration of at least 10 yr. Both urinary albumin to creatinine ratio (ACR) and serum creatinine were positively correlated with adiponectin (Spearman's r = 0.43; P < 0.0001, and r = 0.37; P < 0.0001, respectively) in diabetic subjects. After stratification by albuminuria (normoalbuminuria ACR < 30 mg/g, microalbuminuria ACR = 30-299 mg/g, and macroalbuminuria ACR >or= 300 mg/g), the highest adiponectin concentration was in the macroalbuminuria group (geometric mean = 9.6 microg/ml) and the lowest was in the normoalbuminuric group (geometric mean = 5.6 microg/ml). After adjustment for age, sex, body mass index, and diabetes duration, the serum adiponectin concentration in the macroalbuminuria group was significantly higher than in both other groups (P < 0.0001). Serum adiponectin is lowest in the presence of impaired glucose regulation and early diabetes. In the presence of diabetes, serum adiponectin is positively associated with abnormal renal function and diabetes duration.     

Community acquired, nursing home acquired and hospital acquired pneumonia: A five-year review of the clinical, bacteriological and radiological characteristics

Purpose:

To assess the contemporary clinical, bacteriological and radiographic features of hospitalized patients with community acquired (ca), nursing home acquired (na) and hospital acquired pneumonia (ha) and to examine patient outcome.

Patients and Methods:

All hospital records of patients with pneumonia over a five-year period from April 1987 to March 1992 were reviewed retrospectively. Patients included in the study were all those with a diagnosis of pneumonia as identified by computer records of diagnostic codes at discharge; patients with a specific diagnosis of Pneumocystis carinii pneumonia were excluded. Of 74,435 discharges over the five-year period, 1782 patients met the inclusion criteria.

Results:

Charts of 1622 of the total 1782 cases were reviewed. Mean age was 64.4 years with 59.4% men and 40.6% women. Sixty-three per cent were ca, 28.5% were ha and 8.5% were na. A total of 1542 patients (95%) had at least one concomitant medical condition. Chest roentgenogram was abnormal in 97%. Common organisms isolated overall were Haemophilus influenzae (from 204 patients), Staphylococcus aureas (from 152 patients), Streptococcus pneumoniae (from 143 patients ), Escherichia coli (from 113 patients) and Pseudomonas aeruginosa (from 111 patients). H influenzae and S pneumoniae were most common in ca pneumonia, whereas S aureus and Gram-negative organisms were more common in the ha group and Gram-negative agents in the na group. One hundred and four patients developed complications. Fifteen per cent required intensive care unit admission. The average length of hospitalization in the ca and na groups was 17 days and in the ha group, 43 days. At time of discharge 1261 patients (78%) were cured or improved, and 361 patients (22%) died during the admission.

Conclusions:

These results suggest that hospitalization for pneumonia in the 1990s is primarily for elderly patients with significant co-morbidity. Although microbiology appears unchanged compared with earlier reports, the contemporary population is significantly sicker than previous cohorts. This may account for the persistently high morbidity and mortality despite better or newer antibiotics.     

Isolated thrombocytopenia after allogeneic bone marrow transplantation: existence of transient and chronic thrombocytopenic syndromes

Isolated thrombocytopenia after bone marrow transplantation was investigated in 65 fully engrafted patients surviving at least 60 days posttransplant. Twenty-four patients (37%) developed this complication, which occurred most frequently in patients receiving pretransplant preparation with total body irradiation or busulfan. Two distinct thrombocytopenic syndromes were identified: (1) transient thrombocytopenia (nine patients), in which a normal platelet count (greater than 100,000/microL) was initially established by day +40 but then diminished to less than 10,000 to 45,000/microL on day +40 to +70, with subsequent resolution of the thrombocytopenia by day +90; (2) chronic thrombocytopenia (15 patients), in which a platelet count greater than 100,000/microL was not achieved at any time during the first four months posttransplant, despite the simultaneous presence of normal granulocyte and reticulocyte counts. Although the transient syndrome did not adversely affect prognosis, the chronic syndrome carried a high mortality (21% actuarial survival at 1,000 days posttransplant compared with 67% survival for all patients, P less than .01) and had a high association with both severe (grades 3 to 4) acute graft-versus-host disease (GVHD) and chronic GVHD. In three of nine patients with transient thrombocytopenia, a temporal association with trimethoprim-sulfamethoxazole administration was observed, whereas in all other patients, no drug association could be found. Bone marrow biopsies in those patients with drug-associated thrombocytopenia showed decreased numbers of megakaryocytes, whereas biopsies in the remainder of the transiently thrombocytopenic patients demonstrated adequate numbers of platelet precursors, suggesting peripheral platelet destruction or ineffective thrombopoiesis. Biopsies in the chronic thrombocytopenic patients included those with and without adequate numbers of platelet precursors, although the association with chronic GVHD was strongest in patients demonstrating normal numbers of megakaryocytes. We conclude that isolated thrombocytopenia represents a significant complication of bone marrow transplantation, particularly in patients receiving hematopoietic ablative preparatory regimens, and that it is the chronic, not the transient, thrombocytopenic syndrome that is associated with an adverse patient prognosis.     

Functional and metabolic studies of polymorphonuclear leukocytes in the congenital Pelger-Huet anomaly

Polymorphonuclear leukocytes (PMNL) from two individuals with congenital Pelger-Huet anomaly (PHA) were examined to determine whether functional or metabolic defects accompanied the known morphological abnormality. No abnormalities of the PHA cells, as compared to normal control cells, were found when tested for quantitative leukocyte enzyme activities, nitroblue tetrazolium reduction, hexose monophosphate shunt activity, superoxide production, generation of chemiluminescence, or iodination. The PHA cells, as compared to normal PMNL, demonstrated normal chemotaxis and random migration, as well as bactericidal activity.     

A collaborative, double-blind randomized study of cetiedil citrate in sickle cell crisis

We have recently completed a double-blind, placebo-controlled, noncrossover study, the goal of which was to determine whether cetiedil citrate (cetiedil) could affect the course of vaso-occlusive crises in sickle cell disease. Patients, who presented to the emergency room at least 4 but no more than 24 hours after the onset of a painful vasoocclusive crisis severe enough to require hospitalization, were considered candidates for the study. Each patient received either placebo or cetiedil at one of the following three dosages: 0.2, 0.3, or 0.4 mg/kg body weight. The assigned drug dosage was given as a 30 minute intravenous infusion every 8 hours for 4 consecutive days. A total of 67 patients was enrolled in the study. Cetiedil, at its highest dosage (0.4 mg/kg body weight), was found to be significantly superior to placebo both in reducing the number of painful sites present on all 4 treatment days and in shortening the total time in crisis. No serious adverse reactions were observed during the course of the study. We conclude that cetiedil, given at a dosage of 0.4 mg/kg body weight, is therapeutically advantageous for sickle cell crisis.     

A prospective, randomized study of the use of platelet concentrates irradiated with ultraviolet-B light in patients with hematologic malignancy

BACKGROUND: Irradiation of platelet concentrates (PCs) with ultraviolet- B (UVB) light inactivates the contaminating white cells and might be an alternative to filtration for the prevention of alloimmunization to HLA antigens and subsequent refractoriness to further platelet transfusions in multiply transfused patients with bone marrow failure. STUDY DESIGN AND METHODS: Patients with hematologic malignancy, mainly acute myeloid leukemia, were prospectively assigned in a random manner to receive either UVB-irradiated or control, nonirradiated PCs. All patients were given red cells that were white cell reduced by filtration. Transfusion efficacy and alloimmunization were assessed by means of corrected count increments, requirement for red cells and PCs, and measurement of lymphocyte-reactive antibodies. RESULTS: UVB-irradiated PCs had a clinical efficacy similar to controls as judged by corrected count increments at 1 to 6 and 12 to 24 hours and by the median requirement for red cell and platelet transfusions. Alloimmunization determined by measurements of lymphocyte-reactive antibodies using both conventional and antiglobulin-augmented lymphocytotoxicity techniques was not abolished in recipients of UVB-irradiated PCs (4/30, 13%) but was less than that in controls (5/20, 25%; p = NS). The mean number of platelet transfusion episodes prior to the occurrence of alloimmunization was greater in the control group (27 vs. 10; p = 0.017). CONCLUSION: In this trial, UVB irradiation did not diminish the clinical efficacy of platelet transfusions. There was a small but nonsignificant reduction alloimmunization, but no difference in refractoriness of the two groups was observed. Larger prospective randomized studies are required to confirm these findings and to compare UVB irradiation with white cell reduction.     

干细胞移植治疗缺血性心脏病的进展及其作用机制

学术背景：心肌梗死后，尽管现有的内外科治疗手段可以改善冠状动脉供血、挽救缺血心肌，但对已坏死的心肌或无功能心肌尚无良好治疗措施。细胞作为构成心脏结构、执行心脏功能的物质基础，尽管存在争议，但大量研究资料表明干细胞移植治疗是安全有效的。 目的：文章试图就目前成体干细胞在缺血，陛心脏病治疗的临床研究进展做一综述，客观评价成体干细胞治疗缺血性心脏病的安全性、有效性，阐述成体干细胞改善心功能的可能机制，介绍当今临床研究方向。 检索策略：由该论文的研究人员应用计算机检索Pubmed数据库1996／2007成体干细胞与缺血性心脏病方面的文献，检索词“adult stem cells,ischemial heart disease，cardiomyocytes”，并限定文章语言种类为English。同时计算机检索中国期刊全文数据库1996／2007的相关文献，检索词“成年干细胞，心肌细胞，缺血性心脏病”，并限定文章语言种类为中文。共检索到1303篇文献，对资料进行初审，纳入标准：①文章所述内容应与缺血性心脏病干细胞移植密切相关。②同一领域选择近期发表或在权威杂志上发表的文章。排除标准：①重复性研究。②Meta分析。 文献评价：文献的来源主要是通过对干细胞移植治疗缺血，陛心脏病现状及其作用机制进行汇总分析。1303篇文献中，动物实验和在体、离体、细胞学实验626篇，综述、述评、讲座类文献345篇，临床研究45篇，选用其中的46篇作为本文参考文献。 资料综合：①干细胞为一群具有自我更新、多向分化潜能的原始细胞，分为胚胎干细胞和成体干细胞。虽然研究表明胚胎干细胞较成体干细胞具有更强的增殖和分化潜能，但由于其涉及伦理道德、来源困难等原因，限制了它的使用。②就目前已完成的包括不同类型的成体细胞（如骨髓单个核细胞、内皮祖细胞、CD133^＋细胞、骨髓间充质干细胞、成肌细胞等）移植治疗缺血性心脏病的早期临床试验来看，尽管存在样本小、缺乏随机对照等不足，但均显示一个公认的事实，即无论采用何种方法移植成体干细胞治疗缺血性心脏病均是安全有效的。这对于正在进行的较大规模的临床研究是十分重要的，为其提供了更充分的临床资料。③多数研究认为干细胞改善心功能的作用机制包括直接与间接效应，如移植细胞横向分化为再生心肌与血管、移植细胞的旁分泌作用促进血管再生、抑制心肌细胞凋亡及心室重构等。近来研究认为外源前体移植心肌可以刺激机体内源心肌存留的干细胞增殖，从而改善心功能。 结论：尽管目前成体干细胞改善心功能的确切机制仍不清楚，但多数早期临床研究表明成体干细胞移植治疗缺血性心脏病是安全有效的。当前的研究方向是需要随机、双盲、安慰剂对照的多中心临床试验。     

Antigen-matched donor blood in the transfusion management of patients with sickle cell disease

BACKGROUND: Alloimmunization to red cell antigens is a significant risk in chronically transfused patients with sickle cell disease. Antigen matching, by decreasing the likelihood of alloantibody development, may significantly facilitate long-term management while decreasing morbidity. STUDY DESIGN AND METHODS: The transfusion records of 86 patients who underwent chronic transfusion for sickle cell disease at a tertiary-care medical center were reviewed retrospectively to determine the efficacy of an antigen-matching program in the prevention of alloimmunization to clinically significant red cell antigens. Recipients were phenotyped and given units matched for the K, C, E, S, and Fya or Fyb antigens. RESULTS: None (0%) of the 40 patients who received antigen-matched transfusions showed any evidence of alloimmunization, while 16 (34.8%) of the 46 patients who received both antigen-matched and non-antigen-matched transfusions developed clinically significant alloantibodies. The cost was 1.8 to 1.5 times that for a standard transfusion protocol. CONCLUSION: On the basis of this experience, it is recommended that transfusion centers engaged in the management of chronically transfused sickle cell anemia patients consider providing antigen-matched units for such patients. This is recommended not only because it prevents alloimmunization but also because such a program provides additional clinical benefits to the patient that may outweigh the higher costs of the process.