Potential effectiveness of stored cord blood (non-frozen) for emergency use

Bone marrow has been used for a number of years to assist patients who have accidentally received potentially lethal levels of irradiation. The intent of the transplant is to replace the victim's own bone marrow that has been injured from the irradiation or to act as temporary support to allow the patient's own marrow to recover. Following the Chernobyl disaster, some victims received bone marrow that was HLA matched or partially matched. However, donor marrows were difficult to obtain in adequate numbers; as a substitute for bone marrow, frozen fetal liver cells were used as a source of hematopoietic stem cells. The use of fetal livers, however, was unsuccessful. Human umbilical cord blood, currently considered an excellent source of hematopoietic stem cells, was not used at Chernobyl. For several years, we have been able experimentally to keep SJL/J mice alive with the use of human umbilical cord blood after the animals received lethal levels of irradiation. This finding suggests that under certain conditions human cord blood does not have to be HLA matched to facilitate rescue from irradiation. In addition, there are reports of unmatched HLA cord blood being used successfully for marrow transplantation. If human cord blood does not have to be matched for HLA, there may be emergency cataclysmic circumstances where the availability of umbilical cord blood may be of considerable value. To simulate a clinical situation such as a nuclear accident, in which human cord blood might serve as a source of stem cells for marrow transplantation, we attempted to rescue immunocompetent mice after 900 cGY of irradiation with the use of (nonfrozen) human cord blood stored in a blood bank. The blood was stored under routine conditions (3–6 °C) for 5 and 7 days in special bags that allow transmission of oxygen. Following lethal levels of irradiation, the cord blood was administered to the animals and a significant survival rate was obtained.     

The role of free radicals in endogenous adaptation and intracellular signals

Oxidative stress can generate a mass of oxygen free radicals (OFR) in the cells, and these OFRs can induce several acute and chronic symptoms and diseases. If the amount of the generated OFRs overwhelms the antioxidant capacity of the cells, the pathophysiological changes may lead to the death of the cell or the development of chronic degenerative diseases.     

The final destiny of acantholytic cells in pemphigus is Fas mediated

Background  Pemphigus is an autoimmune disease characterized by the formation of intra-epidermal blisters. Patients develop auto-antibodies against desmoglein 1 and 3 proteins and induce acantholysis.
Objective  This work addresses the issue of whether the Fas pathway mediates acantholysis. Furthermore, the possible suppliers of the Fas pathway were investigated.
Methods  Seventeen biopsies of pemphigus patients were studied by haematoxylin and eosin staining, and apoptosis was defined by TUNEL. The expression of Fas, FasL and caspase 3 was studied by in situ hybridization and immunohistochemistry. Cell infiltrates were studied by immunofluorescence with monoclonal anti-CD3, CD4, CD8, CD19 and CD69.
Results  All of the biopsies showed intra-epidermal blisters, acantholytic cells and inflammatory infiltrates. The blisters expressed Fas, FasL and caspase 3. Cell infiltrates were composed of CD8 and a few CD4⁺CD69⁺ cells. Additionally, CD19⁺ cells were detected. Interestingly, the Fas expression was increased in acantholytic cells and perilesional keratinocytes. Incidentally, these cells exhibited apoptotic features. Interestingly, the CD8 cells expressed FasL.
Conclusion  This paper presents the morphological evidence that apoptosis and acantholysis are linked. Therefore, the Fas pathway is associated with CD8 cells in pemphigus lesions.

Conflicts of interest

None declared.     

Osteoporosis Before Lung Transplantation: Association with Low Body Mass Index, but Not with Underlying Disease

Due to progress in lung transplantation, post-transplantation osteoporosis becomes an important problem. We determined bone mineral density (BMD) in 74 lung transplantation candidates, among them 24 patients with cysticfibrosis, 16 with chronic obstructive pulmonary disease, 14 with pulmonary fibrosis, and 11 with pulmonary hypertension. The mean T score (+/- SD) was -2.6 +/- 1.3 at femoral neck (FN), -2.2 +/- 1.6 at Ward's triangle (WT) and -2.3 +/- 1.5 at lumbar spine (LS). Osteoporosis was found in 61% of the patients at FN, 45% at WT and 50% at LS. Patients with different underlying lung diseases were similarly affected, not only those with cystic fibrosis but also others, including patients with pulmonary hypertension. No association was found between BMD and age, gender, menstrual condition in women and testosterone level in men. A negative correlation was found between chronic glucocorticoid use and T scores. Body mass index correlated positively (p < 0.01) with T scores at any site and the correlation was also significant for the 2 largest subgroups. Loss of lung function (FEV1) also was associated with lower T scores. No correlation was found between BMD and biochemical indices of bone turnover. Multivariate analysis revealed BMI and glucocorticoid use as independent risk factors. We conclude that osteoporosis is a very common condition in patients with end-stage pulmonary disease, independent of the underlying diagnosis. In view of additional bone loss under immunosuppressive treatment after lung transplantation, early diagnosis and prevention of osteoporosis in the pretransplant period should receive high priority.     

Abnormal local-circuit neurons in epilepsia partialis continua associated with focal cortical dysplasia

Summary A limited cortical resection including the rolandic fissure and the pre-and postcentral cortical regions was carried out in a patient suffering from epilepsia partialis continua resistant to antiepileptic drugs. The histological examination revealed several foci of very large neurons distributed with no laminar organization in the depth of the rolandic fissure and in the crown of the primary motor and primary somatosensory areas; these lesions were consistent with focal cortical dysplasia. In addition, decreased numbers of neurons, astrocytosis and proliferation of capillaries, compatible with chronic tissue necrosis, were found in the inferior regions of the banks of the rolandic fissure. Subpopulations of local-circuit neurons were examined with parvalbumin, calbindin D-28k and somatostatin immunocytochemistry. Focal areas of cortical dysplasia contained abnormal immunoreactive neurons. Huge parvalbumin-immunoreactive cells were distributed at random and resembled axo-axonic (chandelier) and basket neurons. Abnormal calbindin D-28k-immunoreactive cells were reminiscent of double-bouquet neurons and multipolar cells. Very large somatostatin-immunoreactive cells were seldom observed in the dysplastic foci. On the other hand, areas of tissue necrosis displayed massive reduction of immunoreactive cells and fibers. Abnormalities in the morphology and distribution of local-circuit (inhibitory) neurons observed here for the first time in focal cortical dysplasia may have a pivotal role in the appearance and prolongation of electrical discharges and continuous motor signs in human focal epilepsy.Supported in part by a grant FIS 90E1263     

Factors Affecting the Risk of Blood Bank Specimen Hemolysis

OBJECTIVES: To evaluate simultaneously several possible risk factors for blood bank specimen hemolysis. METHODS: This was a prospective cohort study of emergency department and labor and delivery patients to estimate the effect of various factors on the risk of blood bank specimen hemolysis. Study variables included patient demographics, type and gauge of needle or catheter, anatomic location of venipuncture, and patient care area. Hemolysis was determined by blood bank laboratory technicians. Cox proportional hazards multivariate regression modeling was performed to estimate the adjusted relative risks for hemolysis. RESULTS: Of the 605 subjects with complete data, 194 (32.1%) subjects had blood specimens drawn directly with a steel needle, and 411 (69.1%) had specimens drawn through a Vialon (BD Medical Systems, Inc., Sandy, UT) intravenous (IV) angiocatheter. The overall risk of hemolysis for all was 7%, 10% for Vialon IV angiocatheters and 1.5% for steel needles. In the multivariate analysis, the factors most closely associated with hemolysis were the use of Vialon IV catheters and sampling from an anatomic site other than the antecubital area. CONCLUSIONS: Blood bank specimens drawn from Vialon IV catheters (particularly smaller gauge catheters) and from veins outside the antecubital area are at significantly increased risk to hemolyze.