Moderate and severe reactions in blood donors

During the period April 1985 to March 1986, 217 blood donors were found to have moderate (syncopal) to severe (convulsive) reactions. This population was compared to 5630 randomly selected donors who did not have reactions. An examination of demographic, physical, and societal/emotional factors was conducted to determine if any were predictive of reactions in donors. The results of the research supported the hypothesis that first-time donors have a higher frequency of reactions (1.7%) than do repeat donors (0.19%). A review of the above predictive factors documented that, with regard to demographic factors, 1) the number of prior donations was inversely proportional to the risk of reaction; 2) the gender of the donor was not predictive; and 3) youth was a predictor of reactions. An analysis of the physical factors revealed that donors who reacted were of lower weight (mean, 153.7 lb) than those who did not (mean, 166.4 lb) and that systolic blood pressure was slightly lower in the group with reactions. Although the difference was significant (3 torr), it was not thought to be significant clinically. In a comparison of a group with systolic blood pressure ranging from 80 to 100 torr and a group with systolic blood pressure ranging from 120 to 140 torr, the first group had a 70-percent higher risk of reaction. Finally, with regard to the last category of societal or emotional factors, the research demonstrates 1) that the ingestion of caffeinated beverages was associated with a reduced risk of reactions; 2) that the food intake of donors who reacred was significantly different from that of those who had no reaction, but this difference was not thought to be clinically significant; and 3) that the duration between registration and the onset of phlebotomy was directly predictive of reaction status. The research indicates that first-time donor status and several specific demographic, physical, and societal or emotional factors are predictors of donor reactions.     

EASE OF HANDLING AND CLINICAL EFFICACY OF FLUTICASONE PROPIONATE ACCUHALER/DISKUS™ INHALER COMPARED WITH THE TURBOHALER™ INHALER IN PAEDIATRIC PATIENTS

A total of 323 children aged 4-11 years who were receiving, or had symptoms indicating a clinical requirement for, inhaled corticosteroid at a daily dose of 400 μg budesonide (BUD) or beclomethasone dipropionate (BDP), or 200 μg fluticasone propionate (FP), were randomised into this multicentre, open-label, parallel group study. Patients received either FP 100 μg b.d. administered via the Accuhaler/Diskus inhaler (n=159) or BUD 200 μg b.d. administered via a Turbohaler inhaler (n=164) for four weeks and recorded daily their morning and evening peak expiratory flow (PEF), asthma symptoms and use of relief medication. Device handling was assessed by a questionnaire, with responses recorded on three- or five-point ordinal scales. The primary efficacy parameter was mean percent predicted morning PEF. The device handling results showed the Accuhaler/Diskus inhaler was rated more favourably than the Turbohaler inhaler in terms of ease of correct inhaler use, ease of telling how many doses were left, ease of knowing whether a dose had been inhaled and overall liking of the device. More patients in the Accuhaler/Diskus group (85%) than in the Turbohaler group (58%) said they would be happy to receive the same device again, while 8% and 25% respectively said they would not be happy to be given it again. In addition, the change from baseline to week 4 of treatment in mean percent predicted morning PEF was greater in the FP Accuhaler/Diskus group, indicating that FP 200 μg daily via Accuhaler/Diskus inhaler is at least as clinically effective as BUD 400 μg daily via the Turbohaler inhaler.     

Protodynamic therapy for bladder cancer: in vitro results of a novel treatment concept

OBJECTIVE

To present a novel treatment approach for urinary bladder cancer, protodynamic therapy, which comprises inhibition of cancer cell proliferation by intracellular acidification; cis‐urocanic acid (cis‐UCA) was investigated as a protodynamic drug in bladder cancer cell cultures and compared with conventional chemotherapeutic agents.

MATERIALS AND METHODS

The moderately differentiated cell line 5637 and the poorly differentiated T24 cell line were exposed to cis‐UCA for 0.25–2 h, and to epirubicin, doxorubicin, cisplatin and paclitaxel for 2 h, to simulate drug exposure on intravesical instillation. The combination of cis‐UCA and chemotherapeutic agents was also studied. Cell viability was measured with a colorimetric assay.

RESULTS

cis‐UCA inhibited proliferation and suppressed the survival of cells at an extracellular pH ≤ pK_a2 of 6.65 but to a lesser degree at pH > pK_a2, as suggested by the protodynamic theory. cis‐UCA caused dose‐dependent, irreversible termination of cell proliferation. The number of viable surviving BC cells decreased by >85% with 2%cis‐UCA (P < 0.001). Viable cells disappeared completely with 4% and 6%cis‐UCA after a 2‐h treatment, and by 90% with 6%cis‐UCA within a 15‐min exposure. These effects were associated with distinct morphological changes. The other drugs tested had a clearly lower effect on cell survival. Interestingly, when combined, cis‐UCA markedly enhanced the cytotoxic effect of epirubicin.

CONCLUSION

cis‐UCA is a potent antiproliferative agent in bladder cancer cell cultures. As our previous non‐clinical studies showed that cis‐UCA is locally and systemically well tolerated, protodynamic therapy with cis‐UCA is a promising intravesical treatment for bladder cancer.     

Effect of caffeine on simulator flight performance in sleep-deprived military pilot students

Caffeine has been suggested to act as a countermeasure against fatigue in military operations. In this randomized, double-blind, placebo-controlled study, the effect of caffeine on simulator flight performance was examined in 13 military pilots during 37 hours of sleep deprivation. Each subject performed a flight mission in simulator four times. The subjects received either a placebo (six subjects) or 200 mg of caffeine (seven subjects) 1 hour before the simulated flights. A moderate 200 mg intake of caffeine was associated with higher axillary temperatures, but it did not affect subjectively assessed sleepiness. Flight performance was similar in both groups during the four rounds flown under sleep deprivation. However, subjective evaluation of overall flight performance in the caffeine group tended to be too optimistic, indicating a potential flight safety problem. Based on our results, we do not recommend using caffeine pills in military flight operations.     

Heart rate and performance during combat missions in a flight simulator

INTRODUCTION: The psychological workload of flying has been shown to increase heart rate (HR) during flight simulator operation. The association between HR changes and flight performance remains unclear. METHODS: There were 15 pilots who performed a combat flight mission in a Weapons Tactics Trainer simulator of an F-18 Hornet. An electrocardiogram (ECG) was recorded, and individual incremental heart rates (deltaHR) from the HR during rest were calculated for each flight phase and used in statistical analyses. The combat flight period was divided into 13 phases, which were evaluated on a scale of 1 to 5 by the flight instructor. RESULTS: HR increased during interceptions (from a mean resting level of 79.0 to mean value of 96.7 bpm in one of the interception flight phases) and decreased during the return to base and slightly increased during the ILS approach and landing. DeltaHR appeared to be similar among experienced and less experienced pilots. DeltaHR responses during the flight phases did not correlate with simulator flight performance scores. Overall simulator flight performance correlated statistically significantly (r = 0.50) with the F-18 Hornet flight experience. CONCLUSIONS: HR reflected the amount of cognitive load during the simulated flight. Hence, HR analysis can be used in the evaluation of the psychological workload of military simulator flight phases. However, more detailed flight performance evaluation methods are needed for this kind of complex flight simulation to replace the traditional but rough interval scales. Use of a visual analog scale by the flight instructors is suggested for simulator flight performance evaluation.     

Job satisfaction, work ability and life satisfaction among Finnish anaesthesiologists

BACKGROUND: Organizational changes and relative growth of the ageing population together with related health problems seem to have increased stressfulness in the work of anaesthesiologists. However, little is known about their work-related well-being and the factors through which their situation could be improved. METHODS: A cross-sectional questionnaire study of the level and the determinants of job satisfaction, work ability and life satisfaction among female and male anaesthesiologists involved 258 Finnish anaesthesiologists working full time (53% men). RESULTS: The respondents had fairly high job satisfaction, work ability and life satisfaction. No gender differences appeared in these well-being indicators, but their determinants differed by gender. Job satisfaction was only associated with work-related factors in both genders: with job control in women and with job control and organizational justice in men. Work ability correlated with job control and health in both genders and with family life in women. Life satisfaction correlated with individual- and family related factors such as social support and family problems in both genders. Life satisfaction correlated with physical workload in men and health in women. Women had less job control, fewer permanent job contracts and more domestic workload than men. CONCLUSIONS: Job control and organizational justice were the most important determinants in work-related well-being. Work-related factors were slightly more important correlates of well-being in males, and family life seems to play a larger role in the well-being of female anaesthesiologists. Organizational and gender issues need to be addressed in order to maintain a high level of well-being among anaesthesiologists.     

Epstein Barr virus latent membrane protein-1 in Hodgkin's lymphoma in Nigerians

Background

The burden of lymphomas on the health care system in Nigeria is enormous. Correct diagnosis and identification of aetiological factor are important steps in reducing this burden.

Methods

Eight cases diagnosed as HL within a period of six years at the Obafemi Awolowo University teaching Hospital, Ile-Ife, Nigeria by haematoxylin and eosin (Hand E) only were immunophenotyped using the indirect immunoperoxidase method. Epstein-Barr virus latent membrane protein-1 (LMP-1), CD15 and CD30 immunohistochemistry was also performed. The clinical characteristics of each patient were documented.

Objectives

To document the frequency of involvement of Epstein-Barr virus in cases of HL seen in a university hospital in Nigeria.

Results

Out of the eight cases diagnosed by H&E as HL immunophenotyping showed only five were HL. The rest were non-Hodgkin''s lymphoma (2 diffuse large B-cell and 1 null cell ALCL). All were cases of classical HL with 60% being of the mixed cellularity (MC) subtype. There were 2 males and 3 females with ages ranging from 7 years to 40 years. All presented with cervical lymphadenopathy and three had splenomegaly in addition. 60% of the tumour was EBV positive, all of the MC subtype. Three patients had chemotherapy. Eventually all were lost to follow-up. There was no case of the nodular lymphocyte predominance variant.

Conclusion

Mixed cellularity is the most common subtype and is the only subtype associated with EBV positivity in this study. Epstein-Barr virus probably plays an important role in the aetiology of HL in Nigerians.Running title: Epstein-Barr virus, Hodgkin''s lymphoma in Nigerians     

Multiple granular cell tumors are an associated feature of LEOPARD syndrome caused by mutation in PTPN11

We report a patient with a clinical and molecular diagnosis of LEOPARD syndrome (LS) associated with multiple granular cell tumors (MGCT). Bidirectional sequencing of exons 7, 12, and 13 of the PTPN11 gene revealed the T468M missense mutation in exon 12. This mutation has been previously reported in patients with LS. To our knowledge, this is the first report of MGCT associated with molecularly characterized LS and provides the first molecular evidence linking granular cell tumors (GCT) to the Ras/mitogen-activated protein (MAP) kinase pathway. We propose that MGCT can be associated with LS. Analysis of GCT from this case tested negatively for loss of heterozygosity (LOH) at the PTPN11 and NF1 loci and did not show deletions of the PTEN gene. The absence of LOH of PTPN11 supports published functional data that T468M is a dominant-negative mutation.