Multiple or uncommon red cell alloantibodies in women: association with autoimmune disease

BACKGROUND: Patients with multiple or uncommon red cell (RBC) alloantibodies require special efforts in the blood bank. This study investigated whether such persons had other immune-related conditions that might help to explain or predict their propensity for RBC antibody formation. STUDY DESIGN AND METHODS: Charts were retrospectively reviewed of 29 men and 83 women with multiple (> or = 3) RBC antibodies of potential clinical significance, uncommon RBC antibodies (anti-e, - Kpb, -Jkb, -Fyb, -S, -U, -Yta, -Dib, -Ata), or both. The clinical features in 43 women with multiple antibodies were compared to those in two equal-sized control cohorts of women matched for transfusion- related diagnoses, but having either one RBC antibody or none. RESULTS: Women with uncommon RBC antibodies had a 33-percent (18/54) prevalence of autoimmune disease. Twenty-eight percent of the 43 women with multiple antibodies had autoimmune disease, compared to 14 percent of women in the cohort with one RBC antibody (p = 0.09) and 7 percent of those in the cohort without RBC antibodies (p = 0.01). Only one of the 29 men had autoimmune disease. CONCLUSION: Autoimmune disease is a common underlying factor in women who make multiple or uncommon RBC alloantibodies of potential clinical significance.     

Therapy of severe aplastic anemia with anti-human thymocyte globulin and androgens: the effect of HLA-haploidentical marrow infusion

Fifty-four patients with severe aplastic anemia were treated with horse anti-human thymocyte globulin (ATG) and androgens. Thirty of these patients also received an infusion of HLA-haploidentical marrow cells. Only those patients having evidence of hematologic recovery within 3 mo after ATG therapy were considered responders to the immunosuppressive regimen. Of 53 patients evaluable for response, 21 had complete or partial responses and 7 had minimal improvement by defined criteria. The remaining patients did not respond or died. Factors correlated with response to therapy included a short duration of aplasia and a high admission granulocyte count. Thirty-six patients (66.7%) are surviving between 18 and 43 mo, and 18 have died. Deaths were due to hemorrhage and/or infection. Short duration of aplasia and high granulocyte counts also correlated with survival, as did younger age. Four patients with complete or partial responses had a recurrence of severe aplasia 6-17 mo after their first course of ATG. Three of these patients were retreated with ATG (and oxymetholone in two cases). All three had second responses to therapy, but two of the three have had second relapses. The fourth patient responded to oxymetholone alone, but died after a second relapse. Mismatched marrow infusion had no effect on the incidence of response or survival.     

Evaluation of the biliary tract: The value of performing magnetic resonance cholangiopancreatography in conjunction with a 3‐D spoiled gradient‐echo gadolinium enhanced dynamic sequence

The 3‐D gradient‐echo (GRE) sequence allows thinner sections and better resolution of biliary obstruction. When the presence of biliary obstruction is identified using magnetic resonance cholangiopancreatography, the addition of the 3‐D GRE sequence may be helpful for diagnosing biliary obstruction. By showing the changes in the bile duct wall, within the duct lumen and around the bile duct, this technique can be helpful for distinguishing benign from malignant stricture as well as a stone from an enhancing intraluminal mass.     

Medication errors in community pharmacy: an investigation into the types and potential causes

Objectives To establish the nature of medication errors occurring within community pharmacy and analyse common error patterns. To identify factors which influence the occurrence of medication errors and near misses, with the intention of designing systems or strategies to reduce the occurrence of these events. Setting Fifteen community pharmacies situated within Brighton and Hove City Primary Care Trust, East Sussex, between January and March 2004. Method A self‐reporting form was designed, piloted and administered to pharmacists, which gathered information on the detection of an error or near miss in the dispensing process. Key findings One‐hundred and thirteen near misses and thirty‐two medication errors were reported. The majority of near misses were detected by the pharmacist at the final check, and the majority of medication errors were detected by the patient or patient's representative. Selection errors were most common, with similar drug names and packaging cited as the main contributory factors. ‘Business’ was frequently cited as the circumstance surrounding the error. Conclusion This study demonstrates that pharmacists do have an important part to play and the positive impact of community pharmacists in preventing, detecting and correcting errors and thus preventing harm to patients in the primary care setting. However, medication errors do occur, and therefore a multifactorial approach by manufacturers, marketing and packaging personnel, in addition to input from pharmacists, may be an effective permanent solution in reducing the errors made.     

Cranial MRI changes may precede symptoms in Hallervorden-Spatz syndrome

Two families are presented in which siblings of children affected with Hallervorden-Spatz syndrome exhibited characteristic cranial magnetic resonance imaging changes before developing clinical features of the disease. Linkage to a major locus on chromosome 20p supported the diagnosis of Hallervorden-Spatz syndrome. In some patients with Hallervorden-Spatz syndrome, iron is radiographically evident before the onset of clinical symptoms.     

中国农村老年人群APOE基因型频率分布研究

目的了解中国农村地区65岁及以上老年人群 APOE 基因型频率分布,为研究 APOE 基因型频率分布与老年人群健康的关系以及开展防治老年性疾病提供科学依据。方法于2004—2008年4月,选择四川省邛崃市与剑阁县、山东省高密市与淄川区农村地区的老年人群(≥65岁)2000人为调查对象。采用 APOE 分型试剂盒对调查对象指血样品进行检测。结果我国农村地区老年人群 APOE 基因型ε2/ε2、ε2/ε3、ε2/ε4、ε3/ε3、ε3/ε4、ε4/ε4的频率依次为1.10%,13.55%,2.05%,68.80%,13.35%和1.15%;ε4携带者(ε2/ε4 ε3/ε4 ε4/ε4)与非ε4携带者(ε2/ε2 ε2/ε3 ε3/ε3)分别为16.55%和83.45%。山东省与四川省农村地区老年人群各 APOE 基因型频率间比较,经 x~2检验,差异均无统计学意义(P>0.05)。结论中国农村地区老年人群 APOEε4基因型频率分布较广。     

Uterine leiomyomas reduce the efficacy of assisted reproduction cycles: results of a matched follow-up study

A matched follow-up study design was used to test the hypothesis that pregnancy rates following assisted reproduction procedures do not differ between women with or without intramural or sub-serosal uterine leiomyomas. Women undergoing their first in-vitro fertilization (IVF)- embryo transfer or zygote intra-Fallopian transfer (ZIFT) cycle between January 1993 and June 1995 were included. Cases (women with leiomyomas) were matched 1:1 with the next consecutive control (women without leiomyomas) according to age, number of embryos transferred, embryo grade, and the route of embryo transfer (uterine or Fallopian). Assisted reproduction cycles were performed in an identical manner, independent of the presence or absence of uterine leiomyomas. The main outcomes measured were clinical pregnancy and delivery rates. A total of 182 cycles was evaluated. Of the 91 assisted reproduction cycles performed in the leiomyoma group, there were 34 clinical pregnancies (37%) and 30 deliveries (33%). Of the 91 assisted reproduction cycles in the control group, there were 48 clinical pregnancies (53%) and 44 deliveries (48%). The Mantel-Haenszel estimate of relative risk indicated that the presence of a uterine leiomyoma significantly reduced the chance for a clinical pregnancy or delivery. These findings suggest that leiomyomas are associated with a reduction in the efficacy of assisted reproduction cycles.      

IsK and KvLQT1: mutation in either of the two subunits of the slow component of the delayed rectifier potassium channel can cause Jervell and Lange-Nielsen syndrome

The Jervell and Lange-Nielsen syndrome (JLNS) comprises profound congenital sensorineural deafness associated with syncopal episodes. These are caused by ventricular arrhythmias secondary to abnormal repolarisation, manifested by a prolonged QT interval on the electrocardiogram. Recently, in families with JLNS, Neyroud et al. reported homozygosity for a single mutation in KVLQT1 , a gene which has previously been shown to be mutated in families with dominantly inherited isolated long QT syndrome [Neyroud et al . (1997) Nature Genet ., 15, 186-189]. We have analysed a group of families with JLNS and shown that the majority are consistent with mutation at this locus: five families of differing ethnic backgrounds were homozygous by descent for markers close to the KVLQT1 gene and a further three families from the same geographical region were shown to be homozygous for a common haplotype and to have the same homozygous mutation of the KVLQT1 gene. However, analysis of a single small consanguineous family excluded linkage to the KVLQT1 gene, establishing genetic heterogeneity in JLNS. The affected children in this family were homozygous by descent for markers on chromosome 21, in a region containing the gene IsK . This codes for a transmembrane protein known to associate with KVLQT1 to form the slow component of the delayed rectifier potassium channel. Sequencing of the affected boys showed a homozygous mutation, demonstrating that mutation in the IsK gene may be a rare cause of JLNS and that an indistinguishable phenotype can arise from mutations in either of the two interacting molecules.      

The amino acid sequence of murine p53 determined from a c-DNA clone

A c-DNA clone containing the complete sequence information for the murine p53 protein, from embryonal carcinoma cells, has been isolated. The nucleotide sequence of this clone reveals an open reading frame encoding a protein of 390 amino acids with a molecular weight of 43,364 Da. The NH2-terminal domain of this protein is acidic whereas the carboxyl terminus is rich in basic amino acid residues. These terminal domains are separated by a proline-rich, hydrophobic run of amino acids. Proline comprises approximately 10% of the total amino acid residues. Two tryptic peptides, derived from p53 protein radiolabeled with either methionine or proline, were purified and the position of these labeled residues in the peptide was determined. The positions of three methionine and five proline residues in these two peptides matched the amino acid sequence of the predicted open reading frame determined from the c-DNA clone.     

A brief overview of the discovery of cell mortality and immortality and of its influence on concepts about aging and cancer

After having accomplished the miraculous performance that led us from conception to birth, then to sexual maturity and adulthood, natural selection failed to develop a more elementary mechanism capable of simply maintaining the results of this process forever. This failure is aging. Because few animals age in the wild, evolution could not give an advantage to animals with modifications due to aging. Natural selection benefits those animals that have the highest likelihood of effectively perpetuating their species because their vital systems have the larger reserve capacity they need to resist and survive predators, disease, injury, and extreme environmental conditions. Natural selection decreases after sexual maturity has been reached because at that stage the species would not derive additional advantages from individuals with larger physiological reserves. A species increases its likelihood of survival by investing its resources and energy into increasing its opportunities for fruitful reproduction rather than into prolonging its postreproductive life span. Most animals are mortal and undergo aging because investment of resources into keeping the body eternally youthful does not promote species survival as much as their investment into strategies that make reproduction more successful.