Two new beta3 integrin mutations in Indian patients with Glanzmann thrombasthenia: localization of mutations affecting cysteine residues in integrin beta3

New mutations in the beta3 integrin subunit have been identified in two unrelated Glanzmann thrombasthenia patients originating from India and Bangladesh. Both patients had histories of excessive bleeding and were found to have Glanzmann thrombasthenia based on absent ADP-induced platelet aggregation. Immunoblotting of platelet lysates of Patient 1 demonstrated reduced levels of alphaIIb and an unexpected high Mr beta3 band of approximately 260,000, with little or no normal-sized beta3. Upon reduction, a weak beta3 band of normal Mr was observed. Platelet lysates of Patient 2 demonstrated undetectable levels of beta3. Sequence analyses identified homozygous mutations in the beta3 genes of both patients. Patient 1 had a C506Y missense mutation resulting in the expression of an unpaired cysteine; we propose that the Mr approximately 260,000 band is a disulfide-bonded beta3 dimer. Patient 2 had an insertion mutation resulting in a frameshift and premature termination. Both mutations affect biogenesis of platelet alphaIIbbeta3 receptors.     

Social Work Admission Assessment Tool for identifying patients in need of comprehensive social work evaluation

Early identification of patients who need a social work evaluation is integral to effective discharge planning. This article describes the development and application of the Social Work Admission Assessment Tool (SWAAT), a six-item scale that identifies patients with complicated discharge needs who require a social work evaluation. It addresses ambulation, mental status, living situation, current social services, self-perceived need for additional services, and need for assistance in going home. Based on their scores, patients are categorized as having low, intermediate, or high need. A greater proportion of high-need patients were discharged with services and had prolonged hospitalizations (p = .0001). The SWAAT is a comprehensive needs assessment tool that may facilitate discharge planning and improve quality of care.     

Dynamics of telomere erosion and its association with genome instability in myelodysplastic syndromes (MDS) and acute myelogenous leukemia arising from MDS: a marker of disease prognosis?

Telomere length was evaluated by terminal repeat fragment method (TRF) in 50 patients with myelodysplastic syndromes (MDS) and acute myelogenous leukemia (AML) arising from MDS and in 21 patients with untreated primary AML to ascertain, whether telomere erosion was associated with progression of MDS towards overt leukemia. Heterogeneity of TRF among MDS FAB subgroups (P=0.004) originated from its shortening in increased number of patients during progression of the disease. Chromosomal aberrations were present in 32% MDS patients with more eroded telomeres (P=0.022), nevertheless a difference between mean TRF in the subgroups with normal and abnormal karyotype diminished during progression of MDS. A negative correlation between individual TRF and IPSS value (P=0.039) showed that telomere dynamics might serve as a useful prognostic factor for assessment of an individual MDS patient's risk and for decision of an optimal treatment strategy.     

Quantitative analysis of DNA levels in maternal plasma in normal and Down syndrome pregnancies

BACKGROUND: We investigated fetal and total DNA levels in maternal plasma in patients bearing fetuses affected with Down syndrome in comparison to controls carrying fetuses with normal karyotype. METHODS: DNA levels in maternal plasma were measured using real-time quantitative PCR using SRY and beta-globin genes as markers. Twenty-one pregnant women with a singleton fetus at a gestational age ranging from 15 to 19 weeks recruited before amniocentesis (carried out for reasons including material serum screening and advanced material age), and 16 pregnant women bearing fetuses affected with Down syndrome between 17 to 22 weeks of gestation were involved in the study. RESULTS: The specificity of the system reaches 100% (no Y signal was detected in 14 women pregnant with female fetuses) and the sensitivity 91.7% (SRY amplification in 22 of 24 examined samples). The median fetal DNA levels in women carrying Down syndrome (n=11) and the controls (n=13) were 23.3 (range 0-58.5) genome-equivalents/ml and 24.5 (range 0-47.5) genome-equivalents/ml of maternal plasma, respectively (P = 0.62). The total median DNA levels in pregnancies with Down syndrome and the controls were 10165 (range 615-65000) genome-equivalents/ml and 7330 (range 1300-36750) genome-equivalents/ml, respectively (P = 0.32). The fetal DNA proportion in maternal plasma was 0%-6 % (mean 0.8%) in women carrying Down syndrome and 0%-2.6 % (mean 0.7 %) in the controls, respectively (P=0.86). CONCLUSIONS: Our study revealed no difference in fetal DNA levels and fetal DNA: maternal DNA ratio between the patients carrying Down syndrome fetuses and the controls.     

Capnography application in acute and critical care

The use of capnography has expanded over recent years. Currently, capnography is used in a variety of acute care settings. This article describes what capnography is and how it is used. The normal and abnormal capnogram or waveforms are described to assist in identifying various clinical situations. The multiplicity of clinical indications include detection of pulmonary embolism as well as malpositioned endotracheal/tracheal, gastric, and small bowel tubes. Capnography also provides clinicians with information regarding expiratory breathing patterns and assists in perfusion assessments such as those for cardiopulmonary resuscitation. Finally, case studies are provided to help the reader apply the concepts of capnography to a variety of acute care settings.     

Levels of testosterone, allopregnanolone and homocysteine in severe hypothyroidism.

Hypothyroidism is very often associated with cardiovascular diseases and neurological complications. Recently, homocysteine has been studied as an independent risk factor for atherosclerosis which negatively affects vascular endothelial cells. Because homocysteine metabolism is related to thyroid and steroid hormones, we studied these relationships in severe hypothyroidism and in euthyroid state. Homocysteine, testosterone and allopregnanolone concentrations were measured in the fasting plasma from 16 women who underwent total thyroidectomy, and who were either hypothyroid or euthyroid. Although all women used oral contraceptives, they were not protected against hyperhomocysteinemia during hypothyroid state. With the normalization of thyroid hormone concentrations homocysteine levels decreased to normal levels. There was a positive correlation between testosterone and homocysteine in the euthyroid state which suggests that not only estrogens but also androgen state should be considered in future studies on homocysteine.     

Bleomycin‐induced chromosomal damage and shortening of telomeres in peripheral blood lymphocytes of incident cancer patients

Disruption of genomic integrity due to deficient DNA repair capacity and telomere shortening constitute hallmarks of malignant diseases. Incomplete or deficient repair of DNA double‐strand breaks (DSB) is manifested by chromosomal aberrations and their frequency reflects inter‐individual differences of response to exposure to mutagenic compounds. In this study, we investigated chromosomal integrity in peripheral blood lymphocytes (PBL) from newly diagnosed cancer patients, including 47 breast (BC) and 44 colorectal cancer (CRC) patients and 90 matched healthy controls. Mutagen sensitivity was evaluated by measuring chromatid breaks (CTAs) induced by bleomycin and supplemented by the chemiluminescent measurement of γ‐H2AX phosphorylation in 19 cancer patients (11 BC, 8 CRC). Relative telomere length (RTL) was determined in 22 BC, 32 CRC, and 64 controls. We observed statistically significant increased level of CTAs (P = .03) and increased percentage of aberrant cells (ACs) with CTAs (P = .05) in CRC patients compared with controls after bleomycin treatment. No differences were observed between BC cases and corresponding controls. CRC and BC patients with shorter RTL (below median) exhibited significantly higher amount of ACs (P = .02), CTAs (P = .02), and cells with high frequency of CTAs (≥12 CTAs/PBL; P = .03) after bleomycin treatment. No such associations were observed in healthy controls. γ‐H2AX phosphorylation after bleomycin treatment in PBL did not differ between CRC and BC patients. Our results suggest that altered DSB repair measured by sensitivity towards mutagen in PBL occurs particularly in CRC carcinogenesis. Irrespective of cancer type, telomere shortening may be associated with a decreased capacity to repair DSB.