Combined iron and zinc supplementation in infants improved iron and zinc status, but interactions reduced efficacy in a multicountry trial in southeast Asia

Deficiencies of iron and zinc are prevalent worldwide. Interactions between these micronutrients therefore have important consequences, also for supplementation. To investigate effects on hemoglobin and zinc concentrations and interactions of iron and zinc supplementation in infants, data from 4 parallel, randomized, placebo-controlled, double-blind trials in Indonesia, Thailand, and Vietnam were pooled. Infants (n=2468), aged 4-6 mo, were supplemented daily with iron (10 mg) and/or zinc (10 mg) for 6 mo. At 3 sites, infants were given vitamin A capsules (VAC) at recruitment. Combined supplementation reduced prevalences of anemia by 21% (P<0.01) and zinc deficiency by 10% (P<0.05) but was less effective (P<0.05) than supplementation with either iron (28% reduction in anemia) or zinc alone (18% reduction in zinc deficiency). Iron reduced the effect of zinc supplementation (interaction P<0.01), but had no separate effect on zinc status, whereas zinc supplementation had a negative effect on hemoglobin concentrations (-2.5 g/L, P<0.001), independent of iron supplementation (Pinteraction=0.25). The effect of iron supplementation on hemoglobin concentrations was almost twice as large in boys than in girls (effect size 12.0 vs. 6.8 g/L, respectively). In infants not receiving iron, VAC administration tended to be associated with lower (3.2%, P=0.07) hemoglobin concentrations. Combined supplementation of iron and zinc was safe and effective in reducing the high prevalences of anemia and iron and zinc deficiencies. Zinc supplementation may negatively affect iron status but iron supplementation does not seem to affect zinc status. Furthermore, VAC administration in the absence of iron supplementation may increase the incidence of anemia.     

Iron deficiency and NRAMP1 polymorphisms (INT4, D543N and 3'UTR) do not contribute to severity of anaemia in tuberculosis in the Indonesian population

Fe-deficiency anaemia is the most common cause of anaemia in developing countries. In these settings, many chronic infections, including tuberculosis (TB), are highly prevalent. Fe is an essential nutrient for both host and mycobacteria that play a pivotal role in host immunity and mycobacterial growth. A case-control study was performed in a TB-endemic region in Jakarta, Indonesia, among 378 pulmonary TB patients and 436 healthy controls from the same neighbourhood with the same socio-economic status. In a number of these subjects the Fe status could be explored. The distribution of three polymorphisms in the natural resistance-associated macrophage protein gene (NRAMP1) including INT4, D543N and 3'UTR was examined for a possible association with susceptibility to TB. Anaemia (corrected for sex) was present in 63.2 % of active TB compared with 6.8 % of controls, with female patients more often affected. Anaemia was more pronounced in advanced TB as diagnosed by chest radiography. Lower Hb concentrations in TB patients were accompanied by lower plasma Fe concentrations, lower Fe-binding capacity and higher plasma ferritin. After successful TB therapy, Fe parameters improved towards control values and Hb levels normalised, even without Fe supplementation. NRAMP1 gene polymorphisms were not associated with TB susceptibility, TB severity or anaemia. In conclusion, most active TB patients had anaemia, which was probably due to inflammation and not to Fe deficiency since TB treatment without Fe supplementation was sufficient to restore Hb concentration.     

The gap between legal rules and practice in advertising non-registered pharmaceutical products : A new method of analysis

The market of non-registered pharmaceutical products is growing fast in number and overall costs, not only in the Netherlands, but also in other European countries. These products often give the impression that the consumer may expect 'an effect as from a drug'. Legally, there is a clear distinction between 'drugs' and 'commodities' in the Netherlands; the question is whether legislation and practice concur. In an investigation we analysed texts of advertisements for non-registered pharmaceutical products published in a popular magazine. A method was developed, based on the legal definition of a drug and jurisprudence, to determine in a qualitative and quantitative way the application of medicinal claims. It transpired that in 65% of the analysed advertisements explicit or implicit claims were made. These products should therefore be subject to drugs legislation. Thus, in the Netherlands there is a gap between legislation and practice in advertising non-registered pharmaceutical products.     

Effects of dopaminergic medications on psychosis and motor function in dementia with Lewy bodies

Dopaminergic treatment in dementia with Lewy bodies (DLB) requires balancing risk of worsened psychosis and potential motor benefit. We assessed the effects of increased dopaminergic medication on psychosis and motor function in DLB. We studied 19 subjects fulfilling probable DLB Consensus criteria before and after increased dopaminergic medications. Standard clinical measures included: Thought Disorder score from the Unified Parkinson's disease Rating Scale (UPDRS) Part I, total motor score (UPDRS Part III), and Hoehn–Yahr (H&Y) stage. Motor benefit defined as >10% improvement over baseline UPDRS Part III score, occurred in only one‐third of subjects. In this group, worsened hallucinations or psychosis developed in one‐third. Considering motor benefit without exacerbation of psychosis as our aim, only 4 DLB subjects (22%) achieved this goal. Our results suggest that dopaminergic medications have limited benefit in DLB because of the low likelihood of motor improvement and the risk of psychosis exacerbation. © 2008 Movement Disorder Society     

Association of <Emphasis Type="Italic">RGS4</Emphasis> variants with schizotypy and cognitive endophenotypes at the population level

Background  

While association studies on schizophrenia show conflicting results regarding the importance of the regulator of the G-protein signaling 4 (RGS4) gene, recent work suggests that RGS4 may impact on the structural and functional integrity of the prefrontal cortex. We aimed to study associations of common RGS4 variants with prefrontal dependent cognitive performance and schizotypy endophenotypes at the population level.     

Osteosarcoma: use of MR imaging and MR spectroscopy in clinical decision making

Magnetic resonance (MR) imaging was performed on 14 patients with histologically proved osteosarcoma (mean age, 14.4 years). There was excellent correlation of intramedullary tumor extent as determined with MR imaging and pathologic examination (r = 99%). This was facilitated by the presence of a chemical shift artifact at the tumor-marrow interface on the T1-weighted images. The correlation between CT and pathologic findings was not as good (r = 84%). In a single patient, however, a 10-cm length of sclerotic bone was incorrectly interpreted as being tumor. If this case is excluded, the correlation between CT and pathologic findings improves significantly (r = 96%). T2-weighted images were optimal in demonstrating soft-tissue bulk and breach of the epiphysis or cortex. Vascular involvement was also readily defined. The T2 value of the tumor soft-tissue component decreased in patients who were deemed to have responded well to therapy. Two patients with very high T2 values after chemotherapy developed wide-spread metastatic disease and died. Phosphorus-31 MR spectroscopy of five patients with osteosarcoma showed elevated levels of phosphomonoesters (PMEs), inorganic phosphate (Pi), and phosphodiesters (PDEs). PME and PDE peak areas decreased in three patients after chemotherapy, while Pi peak areas increased.     

Immunohistochemical evidence for degeneration of cholinergic neurons in the forebrain of the rat following injection of AF64A-picrylsulfonate into the dorsal hippocampus

The cholinergic neurotoxin, AF64A-picrylsulfonate, was unilaterally infused into the dorsal hippocampus of Wistar rats (2 nmol/2 μl/4 min; A 6.2, L^s 1.5, H 6.5, Paxinos and Watson). After 19 days the animals' brains were processed for immunohistochemical staining of choline acetyltransferase (ChAT). Morphometry and counting of ChAT-immunoreactive profiles revealed shrinkage and disappearance of cholinergic neurons in the medial septum and diagonal band of Broca at the lesioned brain side. These data indicate a retrograde degeneration of cholinergic neurons following injection of AF64-A-picrylsulfonate into the dorsal hippocampus of the rat.     

Carotid artery: percutaneous transbrachial selective arteriography with a 4-F catheter

Bilateral selective common carotid artery catheterization was attempted in 72 patients by means of percutaneous placement of a 4-F catheter from a right brachial artery puncture site in the antecubital fossa. The success rate was high (95.8%) and the complication rate low (6.9%), and there were no instances of brachial artery spasm or thrombosis. The experience, while small, suggests that selective common carotid arteriography can be done safely and efficaciously from the right brachial artery approach.     

Silent and humming nasal NO measurements in adults aged 18-70 years

BACKGROUND: The concentration of nitric oxide (NO) measured from the nose is much higher than in the lower airways and increases during humming. We assessed nasal NO (nNO) normal values during breath hold and during humming in healthy adults. MATERIALS AND METHODS: Nasal NO concentrations were measured in healthy adults (ages 18-70). They held their breath for 10 s and thereafter hummed as loud as possible with their mouths closed also for 10 s. During breath hold, air was passively extracted from one nostril with 700 mL min(-1). The average NO concentration at the plateau after 7-10 s was recorded and the mean of three consecutive measurements was calculated. During humming, air was extracted with 1200 mL min(-1), the peak NO values were recorded. RESULTS: One hundred healthy adults participated (37 men). The nNO concentrations during breath hold were distributed normally (mean: 455 parts per billion (p.p.b.), SD 147). A random subgroup of 40 out of the 100 subjects (15 men) performed nNO measurement during humming. The median peak NO value was 1019 p.p.b. (SD 561) at the first, and 837 p.p.b. (SD 408) at the second measurement. There was a significant difference between the peak NO values of first and second humming. CONCLUSION: We present normal values for nNO in adults, which can be used to assess the value of nNO in respiratory illnesses. The peak nNO values during humming are variable, and their clinical relevance remains to be shown.