Immunotoxin treatment targeted to the high-molecular-weight melanoma-associated antigen prolonging the survival of immunodeficient rats with invasive intracranial human glioblastoma multiforme

OBJECT: The aim of this study was to target immunotoxin treatment to the high-molecular-weight melanoma-associated antigen (HMW-MAA) and thereby examine any changes in the survival of immunodeficient rats with human glioblastoma multiforme (GBM). METHODS: To target treatment specifically to human glioma cells, Pseudomonas exotoxin A (PE) was conjugated to the 9.2.27 antibody, which recognizes the HMW-MAA. Treatment of the antigen-positive glioma cell line U87MG with the resulting 9.2.27-PE caused cytotoxicity with a median inhibitory concentration of 1 ng/ml. Intratumoral 9.2.27-PE treatment of intracranial U87MG tumors in nude rats prolonged the survival of these animals by 43% compared with controls. In additional studies on the use of this targeted treatment, the authors precultured freshly dissected glioblastoma multiforme (GBM) biopsy tissue for 1 to 2 weeks. Inoculation of this tissue into the rat brain resulted in diffuse infiltrative gliomas. The markers glial fibrillary acidic protein and S100 protein were found to be expressed in the original biopsy specimens, as well as in the glioma xenografts in nude rat brains. Intratumoral immunotoxin treatment of such established tumors with 9.2.27-PE was effective and prolonged survival time from 30% to as high as 90% in animals with tumors originating from four different GBM specimens. CONCLUSIONS: Targeted treatment of highly invasive GBMs proved effective, and these results emphasize the clinical relevance of this antigen as a target molecule for immunotoxin treatment of human GBMs.     

Low levels of mannose-binding lectin do not affect occurrence of severe infections or duration of fever in acute myeloid leukaemia during remission induction therapy

PURPOSE: To estimate the clinical significance of low serum concentrations of mannose-binding lectin (MBL) in patients with acute myeloid leukaemia (AML) during initial cancer chemotherapy. PATIENTS AND METHODS: 80 consecutive, newly diagnosed, and unselected AML patients (age 18-77 yr) undergoing remission induction chemotherapy. The patients were examined for 28 d. MAIN FINDINGS: Low levels of serum MBL (<1,000 microg/L) were found in 16/80 patients at diagnosis. This frequency is similar to what is found in the general population. In the remaining 64 patients, MBL concentrations were significantly higher than in controls and showed only a slight rise during the period of antineoplastic chemotherapy with its associated infectious complications. Low levels of MBL did not affect overall survival or morbidity in terms of incidence or duration of fever, or occurrence of septicaemia or pneumonia. Long-term survival was likewise independent of MBL concentration. CONCLUSION: MBL levels have no discernible influence on the occurrence or course of infections in AML patients during the initial hospitalisation. The predominant immunodeficiency during this phase is the profound granulocytopenia, which also compromises important effector functions of MBL. The finding in most AML patients of elevated MBL concentrations on admission is most likely because of the role of MBL as an acute phase reactant.     

Dual infections with HIV-1, HIV-2 and HTLV-I are more common in older women than in men in Guinea-Bissau

OBJECTIVES: To investigate the association between the three human retroviruses, HIV-1, HIV-2 and HTLV-I. DESIGN: Community-based follow-up studies of retrovirus infections in two cohorts. METHODS: A total of 2057 individuals aged 35 years and over were eligible for inclusion. Participants were interviewed and had a blood sample drawn. Samples were analysed for HIV-1, HIV-2 and HTLV infections. Uni- and multivariate analyses that included behavioural and socio-economic factors were performed using logistic regression and Poisson regression models. RESULTS: A total of 1686 individuals participated with a blood sample in the HIV prevalence analyses and 1581 individuals participated in the HTLV-I prevalence analyses. The overall prevalence was 2.1% for HIV-1, 13.5% for HIV-2 and 7.1% for HTLV-I. Comparing the < 45 year age group with 45+ year age groups, the female : male (F : M) prevalence ratio increased with age for all three retroviruses. Dual infections were more common in women than in men. Assuming independent distribution of the viruses, the observed prevalence of dual infections in women was significantly higher than expected, while the prevalence was not increased in men. The prevalence of dual infections increased with age in women, the odds ratio (OR) being 3.4 [95% confidence interval (CI), 1.0-11.3] for any combination of dual infection, while the prevalence decreased with age in men (OR, 0.3; 95% CI, 0.1-2.0) (test of interaction, P = 0.033). Control for behavioural factors did not modify these patterns. CONCLUSIONS: The pattern of increased prevalence among older women could have public health implications; women of older age groups should be regarded as a potential vulnerable group and included in HIV/AIDS prevention programmes.     

Post systolic shortening in nonobstructive hypertrophic cardiomyopathy with delayed emptying of the apex: a Doppler flow,tissue Doppler and strain rate imaging case study

We report a case of a 92-year-old woman with syncope and exertional dyspnea, who on echocardiographic examination proved to have hypertrophic cardiomyopathy. Doppler flow revealed delayed emptying of the apex, extending into the early filling phase. Tissue Doppler and strain rate imaging illustrated postsystolic shortening corresponding to the apical ejection, demonstrating that the apical flow was due to wall thickening resulting in active ejection. The imaging methods and mechanics of post-systolic shortening are discussed.     

Effects of cognitive therapy,applied relaxation and nitrous oxide sedation. A five-year follow-up study of patients treated for dental fear

Five years after completing a controlled, randomized treatment trial comparing the effect of nitrous oxide sedation (NO), cognitive therapy (CT), and applied relaxation (AR), all 62 patients who had participated were invited to a follow-up questionnaire study. Forty-three responded. All participants had been to the dentist during the follow-up period. Mean scores (s) on Corah's Dental Anxiety Scale (CDAS) and Symptom Checklist 90 Revised (SCL-90-R, a measure of general psychological distress) were 10.4 (4.1) and 0.35 (0.34), respectively. There were no between-group effects. Significant changes across the assessment phases (at enrollment, after treatment, and 5 years after) were found for both dental fear and general distress (CDAS: F = 137.8, P < 0.01; SCL-90-R: F = 12.5, P < 0.01). However, no significant changes between measures obtained after treatment and at follow-up emerged. Seven participants (3 from the NO group, 2 from the CT group, and 2 from the AR group) had CDAS scores above 14, indicating a recurrent or continual dental fear problem. The majority (81%) assessed the dental fear treatment received 5 years previously to have been useful for them. In conclusion, the favorable effects on dental fear and general psychological distress continued at 5-year follow-up for all treatment groups.     

How to use the world's scarce selenium resources efficiently to increase the selenium concentration in food

The world's rare selenium resources need to be managed carefully. Selenium is extracted as a by-product of copper mining and there are no deposits that can be mined for selenium alone. Selenium has unique properties as a semi-conductor, making it of special value to industry, but it is also an essential nutrient for humans and animals and may promote plant growth and quality. Selenium deficiency is regarded as a major health problem for 0.5 to 1 billion people worldwide, while an even larger number may consume less selenium than required for optimal protection against cancer, cardiovascular diseases and severe infectious diseases including HIV disease. Efficient recycling of selenium is difficult. Selenium is added in some commercial fertilizers, but only a small proportion is taken up by plants and much of the remainder is lost for future utilization. Large biofortification programmes with selenium added to commercial fertilizers may therefore be a fortification method that is too wasteful to be applied to large areas of our planet. Direct addition of selenium compounds to food (process fortification) can be undertaken by the food industry. If selenomethionine is added directly to food, however, oxidation due to heat processing needs to be avoided. New ways to biofortify food products are needed, and it is generally observed that there is less wastage if selenium is added late in the production chain rather than early. On these bases we have proposed adding selenium-enriched, sprouted cereal grain during food processing as an efficient way to introduce this nutrient into deficient diets. Selenium is a non-renewable resource. There is now an enormous wastage of selenium associated with large-scale mining and industrial processing. We recommend that this must be changed and that much of the selenium that is extracted should be stockpiled for use as a nutrient by future generations.     

Spinal substance P release in vivo during the induction of long-term potentiation in dorsal horn neurons

Long-term potentiation (LTP) in wide dynamic range (WDR) neurons in the dorsal horn has been suggested to contribute to central sensitization and the development of chronic pain. Indirect experimental evidence indicates an involvement of substance P (SP), in this respect. The aim of the present study was to monitor the extracellular level of substance P-like immunoreactivity (SP-LI) in the dorsal horn of the rat during and after induction of LTP in WDR neurons in vivo. Electrophysiological recordings of single (WDR) neurons were performed in parallel with microdialysis in the dorsal horn under urethane-anaesthesia. The amount of SP-LI in the microdialysate was determined by radioimmunoassay. As previously shown, high frequency conditioning stimulation of the sciatic nerve induced an increased firing response of WDR neurons. An increased response to C-fibre stimulation, but not A-fibre stimulation, could be determined. A significant increase of the extracellular level of SP-LI in the dorsal horn was detected during, but not after, induction of LTP. These data suggest that SP may be involved in the induction of LTP by high frequency stimulation. However, the maintenance of spinal LTP following high frequency peripheral nerve stimulation does not seem to depend on an increased release of SP.     

Reduced mortality in treating acutely sick,frail older patients in a geriatric evaluation and management unit. A prospective randomized trial

OBJECTIVES: Documentation of treatment effects in acutely sick frail older patients in geriatric evaluation and management units (GEMUs) is scarce. The present study evaluated whether treatment in a GEMU would reduce mortality as compared to traditional treatment delivered in the Department of Internal Medicine. DESIGN: Prospective randomized trial. SETTING: GEMU or general medical ward. PARTICIPANTS: Acutely sick frail patients aged 75 and older who had been admitted to the Department of Internal Medicine were randomly assigned to treatment in the GEMU (n = 127) or to the general medical wards (n = 127). The following inclusion criteria were used to target frail patients: chronic disability, acute impairment of single activity of daily living, mild/moderate dementia, confusion, depression, imbalance/dizziness, falls, impaired mobility, urinary incontinence, malnutrition, polypharmacy, vision or hearing impairment, social problems, or prolonged bedrest. INTERVENTION: In the GEMU, the treatment strategy emphasized interdisciplinary assessment of all relevant disorders, prevention of complications and iatrogenic conditions, early mobilization/rehabilitation, and comprehensive discharge planning. The control group received treatment as usual from the Department of Internal Medicine. After discharge neither group received specific follow-up. MEASUREMENTS: Mortality and causes of death. RESULTS: Mortality in the intervention and control groups, respectively, was 12% and 27% at 3 months (P =.004), 16% and 29% (P =.02) at 6 months, and 28% and 34% (P =.06) at 12 months. The hazard ratio was 0.39 (95% confidence interval = 0.21-0.72) at 3 months. The main cause of death was cardiovascular disease. CONCLUSION: Treatment of acutely sick, frail, older patients in a GEMU substantially reduced mortality.     

Comparison of procedures for evaluating laboratory performance in external quality assessment schemes for lead in blood and aluminum in serum demonstrates the need for common quality specifications

BACKGROUND: The different scoring methods used by eight European External Quality Assessment Schemes (EQASs) for occupational and environmental laboratory medicine were compared to develop suitable quality specifications as a step toward harmonization. METHODS: Real results for blood lead and serum aluminum assays, reported by participants in Italian and United Kingdom EQASs, were evaluated according to individual scheme scoring criteria. The same results were then used to produce z scores using scheme-based between-laboratory SDs as the estimate of variability to determine whether simple performance-derived quality specifications produced better agreement among schemes. RESULTS: The schemes gave conflicting assessments of participants' performance, and participants judged to be successful by one scheme could be defined as performing inadequately by another. An approach proposed by Kenny et al. (Scand J Clin Lab Invest 1999;59:585), which uses clinical inputs to set targets for analytical imprecision, bias, and total error allowable, was then used to elaborate quality specifications. CONCLUSIONS: We suggest that the CLIA '88 recommendations for blood lead (+/- 40 micro g/L or +/- 10% of the target concentration, whichever is the greater) could be used as a quality specification, although a revision to +/- 30 micro g/L or +/- 10% is recommended. For serum aluminum, a suitable quality specification of +/- 5 micro g/L or +/- 20% of the target concentration, whichever is the greater, is suggested. These specifications may be used to compare laboratory performance across schemes.     

Norwegian oncologists' expectations of intensity-modulated radiotherapy

Although intensity-modulated radiotherapy (IMRT) may increase the therapeutic ratio of radiotherapy for a range of malignancies, only a few IMRT treatments have yet been performed in the Nordic countries. The scores derived from a national survey to assess Norwegian oncologists' expectations of IMRT are presented. A questionnaire was distributed to all consultants in oncology at Norwegian radiotherapy clinics. Summary scores of daily general radiotherapy workload (DGRTW), acquaintance with IMRT (AI) and expectations of IMRT (EI) were derived. Thirty-nine questionnaires (67%) were returned from a total of 58 oncologists. The oncologists' scores on the AI scale (mean score: 7.5 out of 21) were rather low. Their AI scores were found to be positively correlated with their DGRTW. Higher scores on the EI scale were documented (mean score: 6.2 out of 14): 15 oncologists (39%) rated IMRT as one of the three major contributors to potentially increased cancer survival. Oncologists treating patients with prostate, head and neck, gastrointestinal and CNS tumours had higher EI scores than the other oncologists (7.7 vs. 5.1; p=0.01). The Norwegian radiation oncologists' expectations of IMRT are high in terms of both the potential clinical benefit and the rate of implementation. This should encourage the radiotherapy communities to continue (or rapidly initiate) their efforts in providing the routines required for safe implementation of IMRT.