Matrix-free calcium in isolated chromaffin vesicles

Isolated secretory vesicles from bovine adrenal medulla contain 80 nmol of Ca2+ and 25 nmol of Mg2+ per milligram of protein. As determined with a Ca2+-selective electrode, a further accumulation of about 160 nmol of Ca2+/mg of protein can be attained upon addition of the Ca2+ ionophore A23187. During this process protons are released from the vesicles, in exchange for Ca2+ ions, as indicated by the decrease of the pH in the incubation medium or the release of 9-aminoacridine previously taken up by the vesicles. Intravesicular Mg2+ is not released from the vesicles by A23 187, as determined by atomic emission spectroscopy. In the presence of N H Q , which causes the collapse of the secretory vesicle transmembrane proton gradient (ApH), Ca2+ uptake decreases. Under these conditions A23 187-mediated influx of Ca2+ and efflux of H+ cease at Ca2+ concentrations of about 4 pM. Below this concentration Ca2+ is even released from the vesicles. At the Ca2+ concentration at which no net flux of ions occurs the intravesicular matrix free Ca2+ equals the extravesicular free Ca2+. In the absence of NH4C1 we determined an intravesicular pH of 6.2. Under these conditions the Ca2+ influx ceases around 0.15 pM. From this value and the known pH across the vesicular membrane an intravesicular matrix free Ca2+ concentration of about 24 pM was calculated. This is within the same order of magnitude as the concentration of free Ca2+ in the vesicles determined in the presence of NH4C1. Calculation of the total Ca2+ present in the secretory vesicles gives an apparent intravesicular Ca2+ concentration of 40 mM, which is a factor of lo4 higher than the free intravesicular concentration of Ca2+. It can be concluded, therefore, that the concentration gradient of free Ca2+ across the secretory vesicle membrane in the intact chromaffin cells is probably small, which implies that less energy is required to accumulate and maintain Ca2+ within the vesicles than was previously anticipated

High-dose therapy and blood or marrow transplantation for non-Hodgkin lymphoma with central nervous system involvement

AbstractThe role of autologous or allogeneic blood or marrow transplantation (BMT) remains undefined in patients with central nervous system (CNS) involvement by lymphoma. The records of all adult and pediatric non-Hodgkin lymphoma patients receiving BMT at Johns Hopkins from 1980 to 2003 were reviewed, and 37 patients were identified who had CNS involvement that was treated into remission by the time of BMT. The chief histologies were diffuse large B-cell lymphoma and T-cell lymphoblastic lymphoma/leukemia. Twenty-four percent received intrathecal chemotherapy alone, and 70% received intrathecal chemotherapy and CNS irradiation before BMT. The main preparative regimens were cyclophosphamide/total body irradiation and busulfan/cyclophosphamide. Forty-one percent received an allogeneic transplant. Lymphoma relapsed after BMT in 14 patients (38%), and at least 5 had documented or suspected CNS relapse. In multivariate models, age ≥18 years at diagnosis, resistant systemic disease, busulfan/cyclophosphamide conditioning, and lack of intrathecal consolidation after BMT were statistically significant predictors of inferior survival. The 5-year actuarial event-free survival was 36%, and overall survival was 39%. After BMT, long-term survival is thus achievable in a subset of patients with a history of treated CNS involvement by non-Hodgkin lymphoma. The survival rates are not dissimilar to those typically seen in other high-risk lymphoma patients undergoing BMT. These data suggest that patients with lymphomatous involvement of the CNS who achieve CNS remission should be offered BMT if it is otherwise indicated

Standardised proformas improve patient handover: Audit of trauma handover practice

<p>Abstract</p> <p>Background</p> <p>The implementation of the European Working Time Directive has meant the introduction of shift patterns of working for junior doctors. Patient handover between shifts has become a necessary part of practice in order to reduce the risk of medical errors. Data handed over between shifts are used to prioritise clinical jobs outstanding, and to create theatre lists. We present a closed-loop audit of handover practice to assess whether standardised proformas improve clinical data transfer between shifts during handover in our Orthopaedic Unit.</p> <p>Methods</p> <p>We collected data handed over between shifts for a period of one week at our department. The data were in the form of hand written data on plain paper used to assist verbal handover. Data were analysed and a standardised handover sheet was trialled. After feedback from juniors the sheet was revised and implemented. A re-audit, of handover data, was then undertaken using the revised standardised proforma during a period of 1 week.</p> <p>Results</p> <p>Forty-eight patients were handed over in week 1 while 55 patients were handed over during re-audit. The standardised proformas encouraged use of pre-printed patient labels which contained legible patient identifiers, use of labels increased from 72.9% to 93.4%. Handover of outstanding jobs increased from 31.25% to 100%. Overall data handed over increased from 72.6% to 93.2%. Handover of relevant blood results showed little improvement from 18.8% to 20.7%</p> <p>Conclusion</p> <p>This audit highlights the issue of data transfer between shifts. Standardised proformas encourage filling of relevant fields and increases the data transferred between shifts thereby reducing the potential for clinical error cause by shift patterns.</p

The workload of web-based consultations with atopic eczema patients at home

Abstract Background Atopic eczema is a chronic inflammatory non-contagious skin disease characterised by intensive itch and inflamed skin. Due to its chronic and relapsing course atopic eczema imposes a great burden on affected families. Review articles about home care telemedicine have indicated advantageous effects of home telehealth. However, few studies have investigated how home care telemedicine applications affect the workload of the clinician. Methods The use of a web-based counselling system was recorded through computerised logging. The doctor who answered the requests sent via the Internet recorded the amount of time needed for reading and answering 93 consecutive requests. Results The time needed by the physician to read and answer a request was less than 5 minutes in 60% of the cases. The doctor spent significantly more time to answer requests that had photographs attached compared to requests without photographs (P = 0.005). The time needed to answer requests received during the winter season (October-March) was significantly longer than the rest of the year (P = 0.023). There was no correlation between the answering time and the age of the patient. Conclusions Individual web-based follow-up of atopic eczema patients at home is feasible. The amount of time needed for the doctor to respond to a request from the patient appears to be small. The answering time seems to depend on whether photographs are supplied and also on seasonal variations of disease activity. Since the management of atopic eczema is complex involving many different types of treatments and educational aspects, we expect this type of communication to be useful also to other chronic disease patients requiring close follow-up.</p

Magnetic field exposure and long-term survival among children with leukaemia

We examined the association between magnetic field (MF) exposure and survival among children with acute lymphoblastic leukaemia (ALL) treated at 51 Pediatric Oncology Group centres between 1996 and 2001. Of 1672 potentially eligible children under treatment, 482 (29%) participated and personal 24-h MF measurements were obtained from 412 participants. A total of 386 children with ALL and 361 with B-precursor ALL were included in the analysis of event-free survival (time from diagnosis to first treatment failure, relapse, secondary malignancy, or death) and overall survival. After adjustment for risk group and socioeconomic status, the event-free survival hazard ratio (HR) for children with measurements ⩾0.3 μT was 1.9 (95% confidence interval (CI) 0.8, 4.9), compared to <0.1 μT. For survival, elevated HRs were found for children exposed to ⩾0.3 μT (multivariate HR=4.5, 95% CI 1.5–13.8) but based on only four deaths among 19 children. While risk was increased among children with exposures above 0.3 μT, the small numbers limited inferences for this finding

The analysis of 2-amino-2-thiazoline-4-carboxylic acid in the plasma of smokers and non-smokers

ATCA (2-amino-2-thiazoline-4-carboxylic acid) is a promising marker to assess cyanide exposure because of several advantages of ATCA analysis over direct determination of cyanide and alternative cyanide biomarkers (i.e. stability in biological matrices, consistent recovery, and relatively small endogenous concentrations). Concentrations of ATCA in the plasma of smoking and non-smoking human volunteers were analyzed using gas-chromatography mass-spectrometry to establish the feasibility of using ATCA as a marker for cyanide exposure. The levels of ATCA in plasma of smoking volunteers, 17.2 ng/ml, were found to be significantly (p < 0.001) higher than that of non-smoking volunteers, 11.8 ng/ml. Comparison of ATCA concentrations of smokers relative to non-smokers in both urine and plasma yielded relatively similar results. The concentration ratio of ATCA for smokers versus non-smokers in plasma and urine was compared to similar literature studies of cyanide and thiocyanate, and correlations are discussed. This study supports previous evidence that ATCA can be used to determine past cyanide exposure and indicates that further studies should be pursued to validate the use of ATCA as a marker of cyanide exposure