CD98: a type II transmembrane glycoprotein expressed from the beginning of primitive and definitive hematopoiesis may play a critical role in the development of hematopoietic cells

In our search for cell surface markers expressed on hematopoietic stem cells and/or very early progenitor cells we found that the Joro 177 monoclonal antibody (MoAb) bound to most hematopoietic cells in day 8/8.5 yolk sac, day 12 fetal liver, and day 13 fetal thymocytes; it stained hematopoietic stem cells and less immature lymphoid, myeloid, and erythroid-lineage cells, but not most thymocytes and splenic lymphocytes in adult mice. Joro 177 MoAb stimulated tyrosine phosphorylation of an integral of 124-kD protein and induced homotypic aggregation of lymphoid progenitor cells. Importantly, Joro 177 MoAb inhibited cell survival/growth and consequently the generation of lymphoid, myeloid, and erythroid lineage cells in vitro from early Lin- hematopoietic precursors. Joro 177 MoAb induced apoptosis of hematopoietic progenitor cells. Molecular cloning and expression indicated that Joro 177 MoAb recognizes a type II transmembrane protein, which is the mouse homologue of the human CD98 heavy chain gene. We suggest that CD98 is a cell membrane receptor involved in the control of cell survival/death of hematopoietic cells.     

Fractionated total-body irradiation and high-dose etoposide as a preparatory regimen for bone marrow transplantation for 94 patients with chronic myelogenous leukemia in chronic phase

Ninety-four consecutive patients with chronic myelogenous leukemia in first clinical chronic phase, median age of 34.0 years (range, 6.8 to 52.4 years), with a histocompatible sibling donor, were treated with fractionated total body irradiation (1,320 cGy) and high-dose etoposide (60 mg/kg) followed by allogeneic bone marrow transplantation (BMT). The median time from diagnosis to BMT was 7.0 months (range, 2.3 to 72.0 months). Sixty patients were treated before BMT with hydroxyurea alone, four patients with busulfan alone, one patient with interferon alone, and the other 29 patients were treated with various combinations of these drugs. Cumulative probabilities of overall survival, event- free survival, and relapse at 5 years were 73%, 64%, and 14%, respectively. The median follow-up time for surviving patients was 38 months, ranging from 12 to 88 months. By stepwise Cox regression analysis, significant prognostic variables were age at transplant, acute graft-versus-host disease > or = grade II, cytomegalovirus- associated interstitial pneumonitis, and years from diagnosis to BMT.     

Comparison of clinical and self-reported diagnoses for participants on a community-based arthritis self-management programme

OBJECTIVE: With the advent of community-based arthritis education programmes, it is important to determine the accuracy of participants' self-reported diagnoses. The purpose of this study was to determine the level of agreement between general practitioner (GP)-recorded and self- reported diagnoses of participants attending an Arthritis Self- Management Programme (ASMP). METHODS: Participants enrolling on the ASMP were asked to (a) identify their type of arthritis via a self- administered postal questionnaire and (b) obtain a written confirmation of their diagnosis from their GP. The sample (n = 613) comprised mainly women (83%) with a mean age of 58.8 yr (S.D. 12.6) and a mean disease duration of 15.4 yr (S.D. 12.5). RESULTS: Participants' self-reported diagnoses were confirmed by GPs in 534 cases [87.1%, 95% confidence interval (CI): 84.4 89.8%]. Confirmed diagnoses were reported by 86.9% (95% CI: 83.1-90.7%) of those with osteoarthritis (OA) and 96.1% (95% CI: 93.6 98.6%) of those with rheumatoid arthritis (RA). The concordance rate for all other types of arthritis combined was lower at 60.5% (95% CI: 49.5-71.5%). There were no significant differences with respect to age, gender, education, physical functioning, duration of disease and number of GP visits between those who correctly identified their type of arthritis and those who did not. CONCLUSIONS: This study suggests that the majority of RA and OA participants attending an arthritis education programme can correctly identify their specific type of arthritis.      

Timing the initiation of renal replacement therapy for acute kidney injury in Canadian intensive care units: a multicentre observational study

Purpose

The optimal timing for starting renal replacement therapy (RRT) in patients with acute kidney injury (AKI) is unknown. Defining current practice is necessary to design interventional trials. We describe the current Canadian practice regarding the timing of RRT initiation for AKI.

Methods

An observational study of patients undergoing RRT for AKI was undertaken at 11 intensive care units (ICUs) across Canada. Data were captured on demographics, clinical and laboratory findings, indications for RRT, and timing of RRT initiation.

Results

Among 119 consecutive patients, the most common ICU admission diagnosis was sepsis/septic shock, occurring in 54%. At the time of RRT initiation, the median and interquartile range (IQR) serum creatinine level was 322 (221-432) ??mol·L^?1. The mean (SD) values for other parameters were as follows: Sequential Organ Failure Assessment (SOFA) score 13.4 (4.1), pH 7.25 (0.15), potassium 4.6 (1.0) mmol·L^?1. Also, 64% fulfilled the serum creatinine-based criterion for Acute Kidney Injury Network (AKIN) stage 3. Severity of illness, measured using Acute Physiology and Chronic Health Evaluation (APACHE II) and SOFA scores, did not correlate with AKI severity as defined by the serum creatinine-based AKIN criteria. Median (IQR) time from hospital and ICU admission to the start of RRT was 2.0 (1.0-7.0) days and 1.0 (0-2.0) day, respectively.

Conclusion

Patients admitted to an ICU who were started on RRT generally had advanced AKI, high-grade illness severity, and multiorgan dysfunction. Also, they were started on RRT shortly after hospital presentation. We describe the current state of practice in Canada regarding the initiation of RRT for AKI in critically ill patients, which can inform the designs of future interventional trials.     

The path of murine serum amyloid a through peritoneal macrophages

Serum amyloid A (SAA) is a family of proteins encoded by four related genes. Of the four, isoforms 1.1 and 2.1 are acute phase proteins synthesized by the liver. They become major components of the HDL plasma fraction during acute tissue injury and the HDL/SAA complex is readily taken up by macrophages. Herein we investigated the path SAA follows when presented to macrophages as HDL/SAA or in liposomes. Using antibodies specific to SAA and confocal microscopy, or EM autoradiography where only SAA is radio-labeled, we show that HDL/SAA is taken up rapidly by macrophages and within 30 min SAA, or fragments thereof, proceeds through the cytoplasm to the peri-nuclear region and then the nucleus. Within 45–60 min SAA, or fragments thereof, is found back in the cytoplasm and at the plasma membrane where it is subsequently extruded. The observation that SAA, or fragments thereof, traverse the nucleus is a novel finding and may implicate SAA in macrophage gene regulation. It also raises questions by what mechanism SAA enters and leaves the nucleus. We further investigated if both SAA isoforms traffic through the macrophage in a similar manner. Isoform differences were observed. Both isoforms bind well to the plasma membrane of macrophages at 4°C, but at 37°C only SAA2.1 is taken up by the cell in significant quantity, and is observed in the nucleus, suggesting that the two isoforms are handled differently and that they may have discrete physiological roles.     

Radical prostatectomy or radiotherapy in carcinoma of prostate. The dilemma continues

Evaluation of the efficacy of radical prostatectomy versus radiotherapy in carcinoma of the prostate has been compromised by the scarcity of data in comparable populations. A nationwide search was conducted to compile the available data on the use of radiotherapy in lymphadenectomy-staged patients. The assessed population consists of patients with tumor confined to the gland (Stages A2 and B), negative staging lymphadenectomy, negative bone scan, and normal serum acid phosphatase level who received external beam radiotherapy with curative intent. To provide a broad spectrum of experiences, the search included patients from a large number of institutions including Stanford University, Washington University (St. Louis), those participating in the Radiation Therapy Oncology Group, and a broad range of radiotherapy practices surveyed by the PCS (Patterns of Care Study). A total of 209 patients were identified. No selection criteria other than the aforementioned were applied. The patients were treated consecutively during the survey period. In sharp contradistinction to the reported results of the VA Uro-Oncology Group the analysis indicates a less than 10 per cent probability of progression within the first five years after completion of treatment. Nationwide, the outcome of radiotherapy-treated patients appears to be equivalent to the comparable surgically treated population.     

Re-assessing accumulated oxygen deficit in middle-distance runners

The purpose of this study was to re-assess the accumulated oxygen deficit (AOD), incorporating recent methodological improvements i.e., 4 min submaximal tests spread above and below the lactate threshold (LT). We Investigated the Influence of the VO2 -speed regression, on the precision of the estimated total energy demand and AOD. utilising different numbers of regression points and including measurement errors. Seven trained middle-distance runners (mean +/- SD age: 25.3 +/- 5.4y, mass: 73.7 +/- 4.3kg. VO2max 64.4 +/- 6.1 mL x kg(-1) x min(-1)) completed a VO2max, LT, 10 x 4 min exercise tests (above and below LT) and high-intensity exhaustive tests. The VO2 -speed regression was developed using 10 submaximal points and a forced y-intercept value. The average precision (measured as the width of 95% confidence Interval) for the estimated total energy demand using this regression was 7.8mL O2 Eq x kg(-1) x min(-1). There was a two-fold decrease in precision of estimated total energy demand with the Inclusion of measurement errors from the metabolic system. The mean AOD value was 43.3 mL O2 Eq x kg(-1) (upper and lower 95% CI 32.1 and 54.5mL o2 Eq x kg(-1) respectively). Converting the 95% CI for estimated total energy demand to AOD or including maximum possible measurement errors amplified the error associated with the estimated total energy demand. No significant difference in AOD variables were found, using 10,4 or 2 regression points with a forced y-intercept. For practical purposes we recommend the use of 4 submaximal values with a y-intercept. Using 95% CIs and calculating error highlighted possible error in estimating AOD. Without accurate data collection, increased variability could decrease the accuracy of the AOD as shown by a 95% CI of the AOD.     

Self-Resolution of Drinking Problems as a Process of Reinvesting in Self

PROBLEM. Resolution of alcohol problems without formal treatment or participation in self-help groups.
METHODS. Qualitative study using grounded theory (N = 11).
FINDINGS. The onset of alcohol problems begins with negligible penalties. Over time, the cost-benefit ratio of drinking habits continues to rise and the risks become too great. Individuals find it necessary to change their drinking patterns by reinvesting in themselves. Assets such as the ongoing availability of information, life-management skills, and self-confidence promote the change process; cultural mores and behaviors of some healthcare providers serve as liabilities. The dividends of self-resolving alcohol problems include self-pride, mental and physical health, conscientious work performance, rewarding relationships, enhancement of creative talents, and spiritual well-being.
CONCLUSIONS. Nurses can play an important role in promoting self-resolution of alcohol problems by providing accurate information and encouraging clients to reinvest in long-standing priorities and values.     

Contribution of skeletal muscle activity to the natural history of acceleration-induced loss of consciousness (G-LOC)

G-LOC and the ensuing incapacitation represents an ever present threat to modern fighter aircraft and aviators. Of the techniques developed to combat gravitational induced stress, particularly such stress acting along the head to foot axis (+Gz), a variety of straining maneuvers have assumed prominence. All the latter techniques involve voluntary skeletal muscle tensing to a varying degree. It is hypothesized that the basis for the importance of skeletal muscle activity in improving G tolerance predominantly lies in the increased muscle spindle afferent activity to the reticular activating system. It is also hypothesized that the natural history of G-LOC can be significantly improved by supplementing muscle spindle activity via active and passive skeletal muscle activity.