Testing the effectiveness of the exercise plus program in older women post-hip fracture

Background: Exercise is an important strategy with potential to improve recovery in older adults following a hip fracture.Purpose: The purpose of this study was to test the impact of a self-efficacy based intervention, the Exercise Plus Program, and the different components of the intervention, on self-efficacy, outcome expectations, and exercise behavior among older women post-hip fracture.Methods: Participants were randomized to one of four groups: exercise plus, exercise only, plus only (i.e., motivation), or routine care. Data collection was done at baseline (within 22 days of fracture), 2, 6, and 12 months post-hip fracture.Results: A total of 209 women were recruited with an average age of 81.0 years (SD=6.9). The majority was White (97.1%), was widowed (57.2%), and had a high school education (66.7%). Generalized Estimating Equations were used to perform repeated measures analyses. No differences in trajectories of recovery were observed for self-efficacy or outcome expectations. A statistically significant difference in the overall trajectory of time in exercise was seen (p<.001), with more time spent exercising in all three treatment groups.Conclusions: The study demonstrated that it was possible to engage these women in a home-based exercise program and that the plus only, exercise only, and the exercise plus groups all increased exercise. Support for this project was provided by National Institute on Aging grants R37 AG09901, R01-AG18668, R01 AG17082, and the Claude D. Pepper Older Americans Independence Center P60-AG12583.     

Role of DAT‐SPECT in the diagnostic work up of Parkinsonism

The diagnosis of idiopathic Parkinson's disease (PD) can be achieved with high degrees of accuracy in cases with full expression of classical clinical features. However, diagnostic uncertainty remains in early disease with subtle or ambiguous signs. Functional imaging has been suggested to increase the diagnostic yield in parkinsonian syndromes with uncertain clinical classification. Loss of striatal dopamine nerve terminal function, a hallmark of neurodegenerative Parkinsonism, is strongly related to decreases of dopamine transporter (DAT) density, which can be measured by single photon emission computed tomography (SPECT). The use of DAT‐SPECT facilitates the differential diagnosis in patients with isolated tremor symptoms not fulfilling PD or essential tremor criteria, drug‐induced, psychogenic and vascular Parkinsonism as well as dementia when associated with Parkinsonism. This review addresses the value of DAT‐SPECT in early differential diagnosis, and its potential as a screening tool for subjects at risk of developing PD as well as issues around the assessment of disease progression. © 2007 Movement Disorder Society     

Synthetic sulpholipopolysaccharides: novel adjuvants for humoral immune responses.

Referring to the strong immunostimulating activity of combinations of lipophilic agents and dextran sulphate, conjugates with chemical determinants of both types of adjuvants were synthesized and then examined for immunostimulatory capabilities in mice. Saturated fatty acids with varying chain lengths and sulphate groups were coupled covalently at defined ratios to the polysaccharide Ficoll (MW 400,000). Chemical analysis of 60 of the sulpholipopolysaccharides synthesized revealed that the number of sulphate groups per monosaccharide unit varied from 0 to 1.6, and the number of lipid groups from 0 to 0.8. Adjuvanticity of these conjugates for the humoral immune response was determined using sheep red blood cells (SRBC) and dinitrophenyl-haptenated bovine serum albumin (DNP-BSA) as antigens. Five days after intraperitoneal injection of adjuvant and antigen, the numbers of direct anti-SRBC plaque-forming cells (PFC) in the spleen were determined. Anti-DNP antibody titres were measured from 1 to 4 weeks after immunization. PFC responses to 2 X 10(6) SRBC were augmented up to a 100-fold by conjugates of Ficoll and sulphate (sulphopolysaccharides: SPs) or lipid groups (lipopolysaccharides: LPs). Introduction of low or moderate numbers of lipid groups in SPs reduced adjuvanticity. Adjuvant activity of sulpholipopolysaccharides (SLPs) with varying sulphate and high lipid content depended on the sulphate contents and the chain length of the lipids. Sulphate reduced adjuvanticity of the SLPs, and the number of sulphate groups required for complete annihilation increased with the chain length of the lipid. LPs and SLPs, including conjugates that did not enhance anti-SRBC PFC responses, augmented serum antibody responses to DNP-BSA while SPs were hardly effective.     

High-risk children in young adulthood: a longitudinal study from birth to 32 years

The developmental courses of high-risk and resilient children were analyzed in a follow-up study of members of a 1955 birth cohort on the island of Kauai, Hawaii. Relative impact of risk and protective factors changed at various life phases, with males displaying greater vulnerability than females in their first decade and less during their second; another shift appears under way at the beginning of their fourth decade. Certain protective factors seem to have a more general effect on adaptation than do specific risk factors.     

Meeting the regulatory requirements for pharmaceutical production of recombinant DNA derived products

Genetic engineering provides the opportunity for the synthesis of human proteins and derivatives thereof which are of significant value for replacement therapy. However, in addition to genetic engineering an extensive process development has to be carried out in order to establish an economic production process and to guarantee consistently high product quality from batch to batch. This includes the characterization of the production host cell vector construct, the validation of the fermentation and the protein purification process as well as the lyophilization and the reconstitution of the final product. A number of in-process and final product controls have to be established and limits for the specification have to be elaborated to provide consistent product quality. Real time stability data have to be supplied because data from accelerated conditions do not allow extrapolation of the shelf life of proteins. Data obtained from process development and validation of the production process contributes to the preparation of the chemical pharmaceutical dossier and the expert report to be submitted to the regulatory authorities.     

Stimulated elastase release from human leukocytes: Influence of anti-asthmatic,anti-inflammatory and calcium antagonist drugsin vitro

In the present study the effects of drugs, with different modes of action, on FMLP-stimulated release of elastase from human leukocytes were investigatedin vitro. Anti-asthmatic and anti-allergic drugs were compared to well-known anti-inflammatory and anti-histamine agents. The anti-asthmatic/anti-allergic compounds azelastine, astemizole and oxatomide, and the 5-lipoxygenase inhibitor NDGA, were able to suppress the release of elastase from human leukocytes in concentrations between 10 and 100 μM. NSAIDs such as indomethacin, diclofenac and piroxicam and the glucocorticoids dexamethasone and hydrocortisone showed little or no activity. The histamine H1 antagonists mepyramine and ketotifen and the calcium antagonists verapamil, nifedipine and TMB-8 were also ineffective in suppressing FMLP-induced elastase release. Reduction in elastase release by azelastine, that accumulates in lung tissue during long-term treatment in animals, may contribute to its anti-inflammatory and anti-allergic effects which are thought to be central to its use in asthma therapy.

     

Machen Arbeitsstoffe herzkrank?

Zusammenfassung Herzkreislauf-Erkrankungen sind die wichtigste Todesursache in den Industrieländern. Anders als die Krebsforschung, vernachlässigt die Herzkreislauf-Forschung bei uns toxische Wirkungen weitgehend, abgesehen von den Genussgiften Nikotin, Koffein, Alkohol, einigen Medikamenten und den (bei uns) arbeitsmedizinischen Randproblemen Schwefelkohlenstoff, Nitratester und Kohlenmonoxid. Es sind aber zahlreiche kardiovaskulärtoxische Arbeitsstoffe bekannt: neben den Genannten auch organische Lösemittel, Metalle, Pestizide, Vinylchlorid, polychlorierte Biphenyle, etc. Ebenso sind verschiedene toxische Wirkmechanismen auf das Herzkreislaufsystem bekannt: z. B. langfristige Entstehung von Arteriosklerose, Bluthochdruck, koronaren Herzerkrankungen, Herzmuskelerkrankungen und Herzrhythmusstörungen. Die Vernachlässigung kardiovaskulär-toxischer Wirkungen widerspricht der Logik; bei vielen Herzkreislauf-Erkrankungen ist eine toxische Mitverursachung plausibel; mit einer weiteren Aufdeckung kardiovaskulär-toxischer Wirkungen ist zu rechnen.

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Summary Cardiovascular diseases are the most important cause of mortality in industrialised countries. Contrary to cancer research, cardiovascular research mostly ignores toxic effects, apart from nicotine, caffeine, alcohol, a few pharmaceutical drugs, and the (in our countries) minor workplace problems carbon disulfide, nitrate esters, and carbon monoxide. But many workplace chemicals are known to be harmful to the cardiovascular system: beside the mentioned, also organic solvents, metals, pesticides, vinylchloride, polychlorinated biphenyles, etc. Several toxic mechanisms in the cardiovascular system are already known: e.g., long-term development of atherosclerosis, hypertension, coronary heart disease, cardiomyopathy, and arrhythmia. To neglect cardiovascular toxicity is contrary to logic; for many cardiovascular diseases toxic effects may be constitutive; more of these effects may be seen in the future.

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Résumé Les maladies cardiovasculaires sont les causes de mort les plus fréquentes dans les pays industrialisés. Contrairement à la recherche sur le cancer, la recherche cardiovasculaire chez nous néglige largement les effets toxiques, à part la nicotine, la caféine, l'alcool, quelques médicaments et les problèmes (chez nous) marginaux de médecine du travail tels que le sulfure de carbone, les esters de nitrate et le monoxyde de carbone. Beaucoup de substances rencontrées sur le lieu de travail sont pourtant connues pour être toxiques pour le système cardiovasculaire: celles déjà citées, les solvants organiques, les métaux, les pesticides, le chlorure de vinyl, les biphényles polychlorés, etc. Plusieurs mécanismes d'action toxique sur le système cardiovasculaires sont également connus, par exemple la formation à longue échéance d'artériosclérose, d'hypertension artérielle, de coronopathies, de cardiomyopathies, de troubles du rythme cardiaque. Négliger la toxicité cardiovasculaire est illogique; les effets toxiques pourraient contribuer à la genèse de beaucoup de maladies cardiovasculaires; la découverte d'autres effets toxiques cardiovasculaires est à prévoir.

     

Isokinetic quadriceps training in patients with patellofemoral pain syndrome

The aims of the present investigation were (a) to evaluate the effect of eccentric quadriceps training in patients with unilateral patellofemoral pain and (b) to compare the effect of eccentric and concentric quadriceps training in patients with bilateral patellofemoral pain. Fifteen patients (9 male and 6 female, aged 17–36 years with a mean of 27.5 years) participated in this study. Nine patients had unilateral pain and trained their painful leg eccentrically, while six had bilateral pain and trained one leg eccentrically and the other concentrically. Quadriceps muscle training was performed on a Kin-Com dynamometer at 90°/s and 120°/s angular velocity twice a week for 8 weeks. Before and after the treatment period the thigh muscle torques were measured on the Kin-Com dynamometer at 60°/s, 90°/s, 120°/s and 180°/s for quadriceps and at 60°/s and 180°/s for hamstrings. Nine controls, matched for gender and age with the group with unilateral pain, were tested in the same way on the Kin-Com dynamometer. For functional evaluation a knee score was calculated before training, after 8 weeks of training and at a mean of 3.4 years after completion of the training. After 8 weeks of training and at follow-up times of 1 and 3.4 years the patients were also questioned regarding whether or not they felt improvement from the training programme. To determine the degree of knee pain during the training Borg's pain scale was used. The results showed that, compared with the controls, the patients had a significantly lower knee extensor torque in their painful leg at all velocities measured. The greatest difference was found during eccentric actions. However, in comparison with the controls there were no significant differences in eccent ic and concentric knee flexor torques. After training there was a significant increase particularly in eccentric but also in concentric torque of the knee extensor in the painful leg of the eccentrically trained group. Of the six patients in the bilateral training group there were five who increased their concentric knee extensor torque and three who increased their eccentric torque. There were no significant differences in concentric and eccentric knee flexor torques before and after training in either of the legs in both training groups. The hamstring/quadriceps ratio was significantly higher in the patients' painful leg before training. However, due to increased quadriceps strength the hamstring/quadriceps ratio dropped after training. Patients in both groups reported no pain or mild pain during the training sessions. The eccentrically trained group was significantly improved both after 8 weeks of treatment and at follow-up 3.4 years later as evaluated using the knee score. The bilaterally trained group was significantly improved 3.4 years after completion of the training programme as evaluated using the knee score.     

Growth effects of epidermal growth factor (EGF) and a monoclonal antibody against the EGF receptor on four glioma cell lines

Summary Epidermal growth factor (EGF) has been shown to stimulate DNA synthesis and cell division in normal glia. At least half of malignant human gliomas (MHG) express high levels of the EGF receptor (EGFR), which are above those detected in normal brain. The demonstration that antibodies against the EGFR inhibit the growth of squamous cell carcinoma line A-431, with large numbers of EGFR, in vitro and in vivo raises the possibility that these agents could be used therapeutically against malignant human gliomas either alone or conjugated to other agents. We have measured the growth effects of EGF and an anti-EGFR monoclonal antibody, 528 (Ab-528), on four well-characterized human malignant glioma cell lines, D-263 MG, D-247 MG, U-343 MGa Cl 26, and D-37 MG, with 2.9×10⁴, 1.5×10⁵, 8.6×10⁵ and 1.59×10⁶ EGFRs per cell, respectively. EGF significantly increased cell number in D-263 MG and D-37 MG by 65% and 74%, respectively, had no effect on D-247 MG, and significantly decreased cell number in U-343 MGa Cl 26 by 39%. U-343 MGa Cl 26 growth was inhibited 19% by Ab-528, but Ab-528 had no effect on growth of the other MHG lines. Ab-528 significantly inhibited all EGF-mediated growth effects. These studies demonstrate that, although Ab-528 alone has little antiproliferative activity on MGH, it successfully competes with EGF to reduce the biological effects of EGF-EGFR binding. Therefore, this antibody could potentially be used to target radioisotopes to MHG via the EGFR for diagnosis and therapy.Supported by Grants CA-11898, NS-20023, CA-43722, and the Association for Brain Tumor Research (MHW, PAH)