No alterations of hippocampal neuronal number and synaptic bouton number in a transgenic mouse model expressing the beta-cleaved C-terminal APP fragment

Previous studies in the literature have resulted in conflicting reports on the potential neurotoxicity of the beta-cleaved Alzheimer's disease C-terminal fragment (beta-CTF) of beta-amyloid precursor protein in vivo. To readdress this question by rigorous quantitative methods, we analyzed transgenic mice expressing human beta-CTF with the I45F mutation (SPA4CT) under control of the prion protein promoter by stereological techniques. The transgene was expressed in hippocampus and cortex in large pyramidal neurons and in dentate gyrus granule cells. Proteolytic processing of beta-CTF released Abeta. However, most of it remained uncleaved. Neurodegeneration was evaluated by investigating the numbers of hippocampal pyramidal and granule neurons, as well as the number of synaptophysin-immunopositive presynaptic boutons in the hippocampus of 15-month-old SPA4CT mice with design-based stereological techniques. The analyses showed that a fourfold higher expression of the transgene compared to murine APP levels had no effect on the numbers of both neurons and synaptophysin-immunopositive presynaptic boutons. These data implicate that expression of beta-CTF per se is not neurotoxic, and that other mechanisms are responsible for the neurotoxic events in Alzheimer's disease brain.     

Do depressive episodes lead to accumulation of vulnerability in the elderly?

The vulnerability-accumulation (or scarring) hypothesis postulates that the experience of depression induces a lasting increase in vulnerability, and through this raises the risk of recurrence. We examined the validity of the vulnerability-accumulation model for depressive episodes in later life. The sample comprised 26 elderly persons who had remitted from a depressive episode and 96 control respondents who were all selected from the participants of a large community survey among persons aged 57 years or more. Several psychosocial vulnerability indicators were assessed premorbidly, during the depressive episode and after remission. High levels of psychological distress, low life satisfaction, chronic somatic diseases, high neuroticism, and low scores on extraversion, mastery, and self-efficacy appeared to be predictors of depression in this sample. During the depressive episode, psychological distress was higher and life satisfaction, physical, role, and social functioning, as well as feelings of self-efficacy lower than before the episode. Physical and role functioning, cognitive function, and self-efficacy were lower after remission compared to premorbid levels, but (other) personality indices had not changed after remission compared to premorbid levels. Furthermore, we failed to find differences between first and recurrent episodes. Support for the vulnerability-accumulation model was limited at the most. Although psychosocial scarring may occur in the elderly, our findings tentatively suggest that this accumulation does not manifest itself in major vulnerability indicators such as neuroticism.     

The spectrum of lower motor neuron syndromes

Abstract. This review discusses the most important lower motor neuron syndromes. This relatively rare group of syndromes has not been well described clinically. Two subgroups can be distinguished: patients in whom motor neurons (lower motor neuron disease (LMND)) are primarily affected or motor axons and their surrounding myelin (multifocal motor neuropathy (MMN)), both leading to muscle atrophy and weakness.Both hereditary and sporadic forms of LMND have been described. The discussion of recent advances in the genetic knowledge of several hereditary forms of LMND may lead to a better understanding of the pathophysiology and the development of therapeutic strategies. By contrast, the pathogenesis of sporadic LMND is largely unknown. It is, therefore, difficult to consider the various sporadic forms of LMND, discussed in this review, as separate diseases. Because the diagnostic and therapeutic options may differ, it would seem rational to consider sporadic LMND as a spectrum of syndromes which can be distinguished from each other on the basis of clinical presentation.MMN is a lower motor neuron syndrome with presumed immunemediated pathogenesis. Evidence of motor conduction block on nerve conduction studies and a positive response to treatment with intravenous immunoglobulins (IVIg) are considered the most relevant criteria for the diagnosis of MMN. As it is treatable, it is important to distinguish MMN from LMND. Careful electrophysiological analysis in the search for conduction block is, therefore, required in all adult patients with pure lower motor neuron syndromes. For the individual patient, dist inction between the various lower motor neuron syndromes is important as it enables the physician to provide adequate information over the disease course in LMND and to facilitate early treatment in MMN.Supported by a grant from the Prinses Beatrix Fonds.     

Does ultrasound disclose a vulnerability factor for Parkinson's disease?

Transcranial ultrasound is a new tool allowing the detection of abnormalities in the echomorphology of the substantia nigra (SN) in patients with Parkinson's disease (PD). Several lines of evidence suggest that the changes in the echo-pattern represent a risk factor as: i) the majority of PD patients exhibit this echo-feature, ii) the presence of such changes in healthy controls is related to a reduced (18)F-Dopa-uptake and clinical signs of nigrostriatal dysfunction. The reason for the change of echogenicity is suggested to be an increased iron content in the substantia nigra causing oxidative stress and neuronal cell damage. This hypothesis of changes in SN echomorphology reflecting a risk factor of PD has to be proved in longitudinal studies.     

Monitoring during cardiac arrest: are we there yet?

Advancements in electronic data acquisition have translated into improved monitoring of victims of cardiac arrest, but initial techniques remain direct observation of pulses and respirations. The most essential monitor continues to be the electrocardiogram. However, monitoring diastolic blood pressure, myocardial perfusion pressure, and end-tidal carbon dioxide are extremely useful. Most of the current research on monitoring during cardiopulmonary resuscitation focuses on methods for analyzing ventricular fibrillation waveforms. By analyzing the waveform, defibrillation shocks may be delivered at the time when the chance of success is optimal. Low-amplitude and low-frequency fibrillation waveforms are associated with increased rates of asystole and pulseless electrical activity after defibrillation. Methods of analyzing the ventricular fibrillation waveform include measuring the amplitude and frequency and combining the contributions of amplitude and frequency by various methods to improve discrimination. Other types of monitoring being studied for their usefulness during cardiac arrests include sonography, Bispectral Index monitoring, tissue carbon dioxide monitors, and pupil observation. The test of these monitoring techniques is ultimately their ability to improve patient survival to hospital discharge, which is a major challenge for resuscitation researchers.     

Health care provider's attitudes and beliefs towards chronic low back pain: the development of a questionnaire

Attitudes and beliefs, or the treatment orientation, of health care providers appear to be important in the management of non-specific chronic low back pain (CLBP). The aims of the current study were two-fold: First of all, the physiotherapists' opinion towards various aspects of the management of CLBP was surveyed. Secondly, in a principal factor analysis, it was investigated whether underlying dimensions could be identified in order to develop the Pain Attitudes and Beliefs Scale for Physiotherapists (PABS_PT). In total, 421 physiotherapists (response rate 62.3%) participated in this study. The results suggested that the majority of physiotherapists hold the opinion that CLBP is not a dangerous condition, that sport should not be discouraged and that patients should not refrain from all physical activity. Moreover physiotherapists seem to hold the opinion that the way patients view their pain influences the progress of symptoms. Finally, physiotherapists seem to hold the opinion that therapy can completely alleviate the functional symptoms and that therapy may have been successful even if pain remains. The principal factor analysis (PAF) yielded an interpretable 2-factor model. Based on highest loading items, factor 1 was labelled 'biomedical orientation', whereas factor 2 was labelled 'behavioural orientation'. The internal consistency (Cronbach's Alpha) of factor 1 was 0.84 and for factor 2, 0.54 explaining 25.2% and 8.2%, respectively, of the total variance. Assessment of the effect of the physiotherapists' characteristics on scores on the different scales was encouraging as results pointed in the directions one would expect. Physiotherapists who attended biopsychosocial education courses had statistically significantly higher scores on the 'behavioural orientation' factor and vice versa. Biomedical specialists scored statistically significantly higher on the 'biomedical orientation' factor. Furthermore, the findings suggested that the PABS_PT discriminates between physiotherapists with a 'behavioural orientation' vs those with a 'biomedical orientation'. To examine the influence of these different treatment orientations with regard to CLBP on patient outcome is a challenge for the near future.     

Prevention of iron deficiency anemia in adolescent and adult pregnancies

OBJECTIVE: Worldwide attention over iron deficiency anemia (IDA) in pregnancy has shifted recently from providing supplements during pregnancy to attempting to ensure that women, especially adolescents, have adequate iron stores prior to conception. We sought to determine whether adolescent and/or adult women still need supplements during pregnancy to avoid IDA, even if iron stores are adequate, and whether the IDA translates into maternal and/or infant morbidity and mortality. DESIGN: Randomized, double-blind clinical trial with placebo control. SETTING: Multicenter clinic setting in central Wisconsin. PARTICIPANTS: Adolescent women 18 years or less in their first pregnancy, and adult women 19 years or older, who were found to be healthy and iron sufficient at their first prenatal visit. METHODS: Participants were randomized to receive iron supplementation (60 mg/day elemental iron) or placebo. Serum ferritin of 12 ng/mL or less with simultaneous hemoglobin of 11 g/dL or less defined IDA. When IDA occurred at the second trimester, a therapeutic supplement of 180 mg of elemental iron per day was initiated. RESULTS: Forty-seven percent of all placebo-supplemented and 16% of all iron-supplemented patients exhibited IDA (p<0.001); 59% of adolescent placebo-supplemented and 20% of adolescent iron-supplemented patients exhibited IDA (p=0.021). Nausea, vomiting, diarrhea, and constipation were not significantly different in the iron supplemented group compared to the placebo group, and no significant differences were seen in maternal or neonatal health, but the number of women studied was limiting for analysis of these adverse events. CONCLUSION: IDA is common in healthy, iron-sufficient adolescent pregnant women during the second trimester, and body stores of iron decline in both adolescent and adult pregnancies. The incidence of IDA during adolescent and adult pregnancies is substantially reduced with 60 mg of elemental iron per day. However, there remains no clear evidence that maternal or neonatal health will benefit from correcting these deficits.     

Evaluation of a new device for home cardiorespiratory recording in children

OBJECTIVE: To evaluate the feasibility of using a new home cardiorespiratory recording device (HCRD) in children. DESIGN: Cross-sectional study. PATIENTS: Consecutive children scheduled for adenotonsillectomy to treat habitual snoring and/or apneas at otorhinolaryngology clinics in 2 academic and 7 general hospitals. INTERVENTION: Single-night unattended home cardiorespiratory recording prior to adenotonsillectomy using the HCRD. MAIN OUTCOME MEASURES: Number of technically acceptable recordings and successful recordings with artifact-free signals (respiration, saturation, and nasal flow) present for sufficient duration to allow scoring of the polysomnogram and to make a diagnosis. RESULTS: Of 53 eligible children, 24 participated in the study. The main reason for nonparticipation was refusal of caregivers (n = 16). Mean (SD) age of participants was 4.2 (1.6) years; median Brouillette obstructive sleep apnea score was 2.54. Technically acceptable recordings were obtained in 18 children (75%). Only 7 recordings (29%) were classified as successful. The poorest signal quality was obtained from the nasal cannula. CONCLUSION: Based on strict scoring criteria in this study, the results of single-night unattended recordings at home with the HCRD fell short of expectations.