Manganese induced brain lesions inMacaca fascicularis as revealed by positron emission tomography and magnetic resonance imaging

A series of positron emission tomography scans was made on two monkeys during a 16-month period when they received manganese(IV)oxide by subcutaneous injection. The distribution of [¹¹C]-nomifensine uptake, indicating dopamine terminals, was followed in both monkey brains. The brain distributions of [¹¹C]-raclopride, demonstrating D₂ dopamine receptors, and [¹¹C]-l-dopa, as a marker of dopamine turnover, were followed in one monkey each. The monkeys developed signs of poisoning namely unsteady gait and hypoactivity. The [¹¹C]-nomifensine uptake in the striatum was reduced with time and reached a 60% reduction after 16 months exposure. This supports the suggestion that dopaminergic nerve endings degenerate during manganese intoxication. The [¹¹C]-l-dopa decarboxylation was not significantly altered indicating a sparing of [¹¹C]-l-dopa decarboxylation during manganese poisoning. A transient decrease of [¹¹C]-raclopride binding occurred but at the end of the study D₂-receptor binding had returned to starting values. The magnetic resonance imaging (MRI) revealed that the manganese accumulated in the globus pallidus, putamen and caudate nucleus. There were also suggestions of gliosis/edema in the posterior limb of the internal capsule. MRI might be useful to follow manganese intoxication in humans as long as the scan is made within a few months of exposure to manganese, i. e. before a reversal of the manganese accumulation.     

Assessment tool for hospital admissions related to medications: development and validation in older patients

International Journal of Clinical Pharmacy - Background Medication-related hospital admissions (MRAs) are frequently used to measure outcomes in studies involving medication reviews. The process of...     

Changes in biochemical markers of bone metabolism and BMD during the first year after a hip fracture

We measured the levels of biochemical markers of bone formation and bone resorption in hip fracture patients preoperatively and after 6 and 12 months. Bone densitometry was done with quantitative computer tomography (QCT), dual-energy X-ray absorptiometry (DXA) and heel ultrasound. After 6 months, the biochemical markers of bone formation and bone resorption had increased. The levels remained high after 1 year and no change occurred between 6 and 12 months. We found no correlations between biochemical bone markers and bone density/ stiffness on admission and change in bone mineral density (BMD) during the first postoperative year, despite the changes in bone markers and bone density. In our opinion, biochemical bone markers can not be used to predict bone loss in the individual patient after a hip fracture.     

Smoking and susceptibility to rheumatoid arthritis in a Swedish population-based case–control study

Smoking is one of the most established risk factors for rheumatoid arthritis (RA). The aim of this study was to estimate how age at smoking debut, smoking cessation, duration, intensity, and cumulative dose of smoking influence the risk of developing anti-citrullinated peptide antibodies (ACPA) positive and ACPA negative RA. The present report is based on a Swedish population-based, case–control study with incident cases of RA (3655 cases, 5883 matched controls). Using logistic regression models, subjects with different smoking habits were compared regarding risk of developing the two variants of RA, by calculating odds ratios (OR) with 95% confidence intervals (CI). Smoking increased the risk of developing both ACPA positive (OR 1.9, 95% CI 1.7–2.1) and ACPA negative RA (OR 1.3, 95% CI 1.2–1.5). For both subsets of RA, there seemed to be a threshold (~ 2.5 pack years for ACPA positive RA and ~ 5 pack years for ACPA negative RA) below which no association between smoking and RA occurred. A dose–response association was observed between cumulative dose of smoking and risk of developing ACPA positive RA (p value for trend < 0.0001). Duration of smoking had a higher influence on the association between smoking and RA than did intensity of smoking. For both subsets of RA, the detrimental effect of smoking decreased after smoking cessation. Twenty years after smoking cessation, there was no longer an association between smoking and risk of ACPA negative RA, whereas the association between smoking and ACPA positive RA risk persisted and was dependent on the cumulative dose of smoking. Smoking increases the risk of both subsets of RA with a more pronounced influence on the risk of ACPA positive RA. Preventive measures in order to reduce smoking are essential and may result in a decline in RA incidence.     

Experimental bacterial meningitis in the rabbit: cerebrospinal fluid changes and its relation to leukocyte response

This study was focused on cerebrospinal fluid (CSF) manifestations in experimental Streptococcus pneumoniae and Escherichia coli meningitis in rabbits. An increased (p less than 0.001) CSF lactate concentration was found in infected animals, mostly not accompanied by a decrease in CSF glucose concentrations. Despite a marked difference in CSF cellular response between the 2 etiological groups no significant difference in CSF lactate levels was found. Neither did CSF lactate levels correlate to CSF polymorphonuclear cell counts. CSF concentrations of albumin were with large variations above control levels in all infected animals. Also a small or moderate increase in CSF albumin levels was generally associated with a marked increase in CSF lactate concentration. The concentration of total amino acids in the CSF was above control values (mean + 2 SD) in 9/21 infected animals. Halothane/N2O anesthesia for 25 min increased (p less than 0.05) CSF levels of glucose, partly independent of alterations in plasma glucose concentrations, in both infected rabbits and in controls.     

Treatment of anaerobic infections with metronidazole.

Metronidazole (Flagl), a compound widely used in man with minimal side-effects, has been used in the treatment of anaerobic infections caused by Bacteroides fragilis and other Bacteroides species. Seven patients were treated and all were restored to full health. Four of them did not respond to lincomycin or clindamycin which so far have been the drugs of choice against anaerobic infections. The reasons for the good results during metronidazole therapy such as the good penetration through the blood/brain barrier and into abscess cavities are discussed.     

Semi-automatic quantification of myocardial infarction from delayed contrast enhanced magnetic resonance imaging

OBJECTIVE: Accurate and reproducible assessment of myocardial infarction is important for treatment planning in patients with ischemic heart disease. This study describes a novel method to quantify myocardial infarction by semi-automatic delineation of hyperenhanced myocardium in delayed contrast enhanced (DE) magnetic resonance (MR) images. DESIGN: The proposed method automatically detects the hyperenhanced tissue by first determining the signal intensity of non-enhanced myocardium. A fast level set algorithm was used to limit the heterogeneity of the hyperenhanced regions, and to exclude small regions that constitute noise rather than infarction. The method was evaluated in 40 patients; 20 with acute infarction and 20 with chronic healed infarction using scanners from two different manufacturers. Infarct size measured by the proposed semi-automatic method was compared with manual measurements from three experienced observers. The software used is freely available for research purposes at http://segment.heiberg.se. RESULTS: The difference in infarct size between semi-automatic quantification and the mean of the three observers was 6.1+/-6.6 ml (mean+/-SD), and the interobserver variability (SD) was 4.2 ml. CONCLUSIONS: The method presented is a highly automated method for analyzing myocardial viability from DE-MR images. The bias of the method is acceptable and the variability is in the same order of magnitude as the interobserver variability for manual delineations.     

Nutritional treatment of bone fracture

PURPOSE OF REVIEW: Osteoporosis and sarcopenia are nutrition-related risk factors for bone fracture and delayed recuperation from fracture. The purpose of this review was to summarize recent studies that evaluated the effect of the nutritional or anabolic treatment of patients with osteoeporotic, e.g. hip, fractures. RECENT FINDINGS: Four short-term supplementation trials reported trends for improved nutritional and functional status. A high dropout rate and low compliance contributed to negative deductions. The latest Cochrane update on hip fracture aftercare sticks to its previous conclusion that multinutrient feeds reduce the incidence of unfavourable outcomes, i.e. mortality and complications combined. Nandrolone in combination with liquid supplementation improved lean body mass, activities of daily living function and quality of life, effects reported to be partly similar for growth hormone treatment. Bone resorption decreased on 12 months' liquid supplementation in community dwelling osteoporotic individuals. A high protein intake was associated with a lower risk of hip fracture. Calcium and vitamin D supplementation remain the basic prevention for osteoporotic fractures. SUMMARY: Recent supplementation studies appeared to be underpowered or suffered logistic problems, but previous recommendations for multinutrient feeding in hip fracture aftercare remain. Supplementation trials of higher scientific quality are needed, and enteral feeding, anabolic treatment and multimodal approaches need to be evaluated further.     

Effects of manganese oxide on monkeys as revealed by a combined neurochemical,histological and neurophysiological evaluation

Four monkeys were exposed to a total of 8 g each of manganese as oxide by repetitive subcutaneous injections during 5 months, after which they were left for 1 week to 6 months before they were sacrificed. All animals developed hyperactive behaviour after about 2 months. About 5 months after the start of the exposure the animals became hypoactive with an unsteady gait, and subsequently an action tremor appeared in some of the animals. The animals lost power in both upper and lower limbs and the movements of the hands and feet were very clumsy. The serum content of manganese rose 10–40 times during the exposure time and the content in brain was generally increased more than 10 times, with the highest content found in globus pallidus and putamen. The observed neurochemical effects were also largest in globus pallidus and putamen. In these regions there was a considerable depletion of dopamine and 3,4-dihydroxyphenylacetic acid, while the homovanillic acid content remained almost unchanged. A severe neuronal cell loss was observed in globus pallidus but not in other regions. This is in accordance with results from the most recent neuropathological study of a human suffering from chronic manganese poisoning [Yamada et al. (1986) Acta Neuropathol 70: 273–278] where globus pallidus was devoid of neuronal cells while the content of pigmented cells in substantia nigra was normal. Our data suggest a reduction in number of dopaminergic nerve terminals, as the activity of the dopamine synthesizing enzyme DOPA-decarboxylase was also lowered. In addition to the effects on the dopaminergic system, a reduced content of 5-hydroxyindole acetic acid was observed in the putamen and globus pallidus. Moreover neurotensin, a neuropeptide with functional connection to the dopaminergic system, was found to be reduced in the putamen. It was remarkable that all the neurochemical effects seen in the putamen were more or less absent from the caudate nucleus. These observations are discussed in relation to what has been found in Parkinsonian and MPTP-lesioned brains.