Anti-Müllerian hormone: A function beyond the Müllerian structures.

The anti-Müllerian hormone (AMH) is a heterodimeric glycoprotein belonging to the TGFb superfamily implicated in human embryonic development. This hormone was first described as allowing regression of the epithelial embryonic Müllerian structures in males, which would otherwise differentiate into the uterus and fallopian tubes. It activates a signaling pathway mediated by two transmembrane receptors. Binding of AMH to its receptor induces morphological changes leading to the degeneration of Müllerian ducts. Recently, new data has shown the role played by this hormone on structures other than the genital tract. If testicular AMH expression decreases in humans over the course of a lifetime, synthesis may persist in other tissues in adulthood. The mechanisms underlying its production have been unveiled. The aim of this review is to describe the different pathways in which AMH has been identified and plays a pivotal role.

Implementing guidelines and training initiatives to improve cross-cultural communication in primary care consultations: a qualitative participatory European study.

BACKGROUND: Cross-cultural communication in primary care is often difficult, leading to unsatisfactory, substandard care. Supportive evidence-based guidelines and training initiatives (G/TIs) exist to enhance cross cultural communication but their use in practice is sporadic. The objective of this paper is to elucidate how migrants and other stakeholders can adapt, introduce and evaluate such G/TIs in daily clinical practice. METHODS: We undertook linked qualitative case studies to implement G/TIs focused on enhancing cross cultural communication in primary care, in five European countries. We combined Normalisation Process Theory (NPT) as an analytical framework, with Participatory Learning and Action (PLA) as the research method to engage migrants, primary healthcare providers and other stakeholders. Across all five sites, 66 stakeholders participated in 62 PLA-style focus groups over a 19 month period, and took part in activities to adapt, introduce, and evaluate the G/TIs. Data, including transcripts of group meetings and researchers' fieldwork reports, were coded and thematically analysed by each team using NPT. RESULTS: In all settings, engaging migrants and other stakeholders was challenging but feasible. Stakeholders made significant adaptations to the G/TIs to fit their local context, for example, changing the focus of a G/TI from palliative care to mental health; or altering the target audience from General Practitioners (GPs) to the wider multidisciplinary team. They also progressed plans to deliver them in routine practice, for example liaising with GP practices regarding timing and location of training sessions and to evaluate their impact. All stakeholders reported benefits of the implemented G/TIs in daily practice. Training primary care teams (clinicians and administrators) resulted in a more tolerant attitude and more effective communication, with better focus on migrants' needs. Implementation of interpreter services was difficult mainly because of financial and other resource constraints. However, when used, migrants were more likely to trust the GP's diagnoses and GPs reported a clearer understanding of migrants' symptoms. CONCLUSIONS: Migrants, primary care providers and other key stakeholders can work effectively together to adapt and implement G/TIs to improve communication in cross-cultural consultations, and enhance understanding and trust between GPs and migrant patients.

Peroxisome proliferator-activated receptor alpha (PPARalpha) protects against oleate-induced INS-1E beta cell dysfunction by preserving carbohydrate metabolism.

AIMS/HYPOTHESIS: Pancreatic beta cells chronically exposed to fatty acids may lose specific functions and even undergo apoptosis. Generally, lipotoxicity is triggered by saturated fatty acids, whereas unsaturated fatty acids induce lipodysfunction, the latter being characterised by elevated basal insulin release and impaired glucose responses. The peroxisome proliferator-activated receptor alpha (PPARalpha) has been proposed to play a protective role in this process, although the cellular mechanisms involved are unclear. METHODS: We modulated PPARalpha production in INS-1E beta cells and investigated key metabolic pathways and genes responsible for metabolism-secretion coupling during a culture period of 3 days in the presence of 0.4 mmol/l oleate. RESULTS: In INS-1E cells, the secretory dysfunction primarily induced by oleate was aggravated by silencing of PPARalpha. Conversely, PPARalpha upregulation preserved glucose-stimulated insulin secretion, essentially by increasing the response at a stimulatory concentration of glucose (15 mmol/l), a protection we also observed in human islets. The protective effect was associated with restored glucose oxidation rate and upregulation of the anaplerotic enzyme pyruvate carboxylase. PPARalpha overproduction increased both beta-oxidation and fatty acid storage in the form of neutral triacylglycerol, revealing overall induction of lipid metabolism. These observations were substantiated by expression levels of associated genes. CONCLUSIONS/INTERPRETATION: PPARalpha protected INS-1E beta cells from oleate-induced dysfunction, promoting both preservation of glucose metabolic pathways and fatty acid turnover.

The transcription factor PAX4 acts as a survival gene in INS-1E insulinoma cells.

The paired/homeodomain transcription factor Pax4 is essential for islet beta-cell generation during pancreas development and their survival in adulthood. High Pax4 expression was reported in human insulinomas indicating that deregulation of the gene may be associated with tumorigenesis. We report that rat insulinoma INS-1E cells express 25-fold higher Pax4 mRNA levels than rat islets. In contrast to primary beta-cells, activin A but not betacellulin or glucose induced Pax4 mRNA levels indicating dissociation of Pax4 expression from insulinoma cell proliferation. Short hairpin RNA adenoviral constructs targeted to the paired domain or homeodomain (viPax4PD and viPax4HD) were generated. Pax4 mRNA levels were lowered by 73 and 50% in cells expressing either viPax4PD or viPax4HD. Transcript levels of the Pax4 target gene bcl-xl were reduced by 53 and 47%, whereas Pax6 and Pdx1 mRNA levels were unchanged. viPax4PD-infected cells displayed a twofold increase in spontaneous apoptosis and were more susceptible to cytokine-induced cell death. In contrast, proliferation was unaltered. RNA interference-mediated repression of insulin had no adverse effects on either Pax4 or Pdx1 expression as well as on cell replication or apoptosis. These results indicate that Pax4 is redundant for proliferation of insulinoma cells, whereas it is essential for survival through upregulation of the antiapoptotic gene bcl-xl.

Using Participatory Learning & Action (PLA) research techniques for inter-stakeholder dialogue in primary healthcare: an analysis of stakeholders' experiences.

PLAIN ENGLISH SUMMARY: It is important for health care workers to know the needs and expectations of their patients. Therefore, service users have to be involved in research. To achieve a meaningful dialogue between service users, healthcare workers and researchers, participatory methods are needed. This paper describes how the application of a specific participatory methodology, Participatory Learning and Action (PLA) can lead to such a meaningful dialogue. In PLA all stakeholders are regarded as equal partners and collaborators in research.During 2011-2015, a European project called RESTORE used PLA in Austria, Greece, Ireland, The Netherlands and the UK to investigate how communication between primary health care workers and their migrant patients could be improved.Seventy eight migrants, interpreters, doctors, nurses and other key stakeholders (see Table 2) participated in 62 PLA sessions. These dialogues (involving discussions, activities, PLA techniques and evaluations) were generally 2-3 h long and were recorded and analysed by the researchers.Participants reported many positive experiences about their dialogues with other stakeholders. There was a positive, trusting atmosphere in which all stakeholders could express their views despite differences in social power. This made for better understanding within and across stakeholder groups. For instance a doctor changed her view on the use of interpreters after a migrant explained why this was important. Negative experiences were rare: some doctors and healthcare workers thought the PLA sessions took a lot of time; and despite the good dialogue, there was disappointment that very few migrants used the new interpreting service. ABSTRACT: Background In order to be effective, primary healthcare must understand the health needs, values and expectations of the population it serves. Recent research has shown that the involvement of service users and other stakeholders and gathering information on their perspectives can contribute positively to many aspects of primary healthcare. Participatory methodologies have the potential to support engagement and dialogue between stakeholders from academic, migrant community and health service settings. This paper focuses on a specific participatory research methodology, Participatory Learning and Action (PLA) in which all stakeholders are regarded as equal partners and collaborators in research.Our research question for this paper was: "Does the application of PLA lead to meaningful engagement of all stakeholders, and if so, what elements contribute to a positive and productive inter-stakeholder dialogue?". Methods We explored the use of PLA in RESTORE, a European FP7-funded project, during 2011-2015 in 5 countries: Austria, Greece, Ireland, the Netherlands and the UK. The objective of RESTORE was to investigate and support the implementation of guidelines and training initiatives (G/TIs) to enhance communication in cross-cultural primary care consultations with migrants.Seventy eight stakeholders (migrants, interpreters, doctors, nurses and others - see Table 2) participated in a total of 62 PLA sessions (discussions, activities, evaluations) of approximately 2-3 h' duration across the five sites. During the fieldwork, qualitative data were generated about stakeholders' experiences of engagement in this dialogue, by means of various methods including participatory evaluations, researchers' fieldwork reports and researcher interviews. These were analysed following the principles of thematic analysis. Results Stakeholders involved in PLA inter-stakeholder dialogues reported a wide range of positive experiences of engagement, and very few negative experiences. A positive atmosphere during early research sessions helped to create a sense of safety and trust. This enabled stakeholders from very different backgrounds, with different social status and power, to offer their perspectives in a way that led to enhanced learning in the group - they learned with and from each other. This fostered shifts in understanding - for example, a doctor changed her view on interpreted consultations because of the input of the migrant service-users. Conclusion PLA successfully promoted stakeholder involvement in meaningful and productive inter-stakeholder dialogues. This makes it an attractive approach to enhance the further development of health research partnerships to advance primary healthcare.

Long-chain fatty acids inhibit acetyl-CoA carboxylase gene expression in the pancreatic beta-cell line INS-1.

The mechanism whereby long-term exposure of the beta-cell to fatty acids alters the beta-cell response to glucose is not known. We hypothesized that fatty acids may alter beta-cell function by changing the expression level of metabolic enzymes implicated in the regulation of insulin secretion, in particular acetyl-CoA carboxylase (ACC). This enzyme catalyzes the formation of malonyl-CoA, a key regulator of fatty acid oxidation. Using the beta-cell line INS-1 as a model, the results show that the polyunsaturated fatty acid linoleate (C18:2) inhibited both basal and glucose-stimulated ACC mRNA induction. The inhibition was detected by 4-6 h, and a maximal 60% effect occurred at 12 h after cell exposure to the fatty acid. Linoleate, as glucose, did not modify the half-life of the ACC transcript. Prolonged exposure of INS-1 cells to linoleate also inhibited ACC protein accumulation at low and high glucose. The saturated fatty acids myristate (C14:0), palmitate (C16:0), and stearate (C18:0) were also effective as well as the monounsaturated oleate (C18:1) and the short-chain fatty acids butyrate (C4:0) and caproate (C6:0); long-chain omega3 fatty acids were ineffective. The threshold concentration for long-chain fatty acids was 0.05 mmol/l, and maximal inhibition occurred at 0.3 mmol/l. 2-bromopalmitate, a nonmetabolizable analog, had no effect, suggesting that fatty acids must be metabolized to change ACC gene expression. Prolonged exposure of INS-1 cells to palmitate, oleate, and linoleate markedly altered the glucose-induced insulin response, resulting in high basal insulin release and a suppression of glucose-induced insulin secretion. This was associated with an exaggerated (twofold to threefold) rate of fatty acid oxidation at all tested glucose concentrations. The data provide a possible mechanism to at least partially explain how fatty acids cause beta-cell insensitivity to glucose, i.e., by downregulating ACC with a resulting exaggerated fatty acid oxidation.

Evidence for an anaplerotic/malonyl-CoA pathway in pancreatic beta-cell nutrient signaling.

A metabolic model of fuel sensing has been proposed in which malonyl-CoA and long-chain acyl-CoA esters may act as coupling factors in nutrient-induced insulin release (Prentki M, Vischer S, Glennon MC, Regazzi R, Deeney J, Corkey BE: Malonyl-CoA and long chain acyl-CoA esters as metabolic coupling factors in nutrient-induced insulin secretion. J Biol Chem 267:5802-5810, 1992). To gain further insight into the control of malonyl-CoA content in islet tissue, we have studied the short- and long-term regulation of acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) in the beta-cell. These enzymes catalyze the formation of malonyl-CoA and its usage for de novo fatty acid biogenesis. ACC mRNA, protein, and enzymatic activity are present at appreciable levels in rat pancreatic islets and clonal beta-cells (HIT cells). Glucose addition to HIT cells results in a marked increase in ACC activity that precedes the initiation of insulin release. Fasting does not modify the ACC content of islets, whereas it markedly downregulates that of lipogenic tissues. This indicates differential regulation of the ACC gene in lipogenic tissues and the islets of Langerhans. FAS is very poorly expressed in islet tissue, yet ACC is abundant. This demonstrates that the primary function of malonyl-CoA in the beta-cells is to regulate fatty acid oxidation, not to serve as a substrate for fatty acid biosynthesis. The anaplerotic enzyme pyruvate carboxylase, which allows the replenishment of citric acid cycle intermediates needed for malonyl-CoA production via citrate, is abundant in islet tissue. Glucose causes an elevation in beta (HIT)-cell citrate that precedes secretion, and only those nutrients that can elevate citrate induce effective insulin release. The results provide new evidence in support of the model and explain why malonyl-CoA rises markedly and rapidly in islets upon glucose stimulation: 1) glucose elevates citrate, the precursor of malonyl-CoA; 2) glucose enhances ACC enzymatic activity; and 3) malonyl-CoA is not diverted to lipids. The data suggest that ACC is a key enzyme in metabolic signal transduction of the beta-cell and provide evidence for the concept that an anaplerotic/malonyl-CoA pathway is implicated in insulin secretion.

Long-term exposure of beta-INS cells to high glucose concentrations increases anaplerosis, lipogenesis, and lipogenic gene expression.

Chronic exposure of pancreatic beta-cells to high glucose has pleiotropic action on beta-cell function. In particular, it induces key glycolytic genes, promotes glycogen deposition, and causes beta-cell proliferation and altered insulin secretion characterized by sensitization to low glucose. Postglycolytic events, in particular, anaplerosis and lipid signaling, are thought to be implicated in beta-cell activation by glucose. To understand the biochemical nature of the beta-cell adaptive process to hyperglycemia, we studied the regulation by glucose of lipogenic genes in the beta-cell line INS-1. A 3-day exposure of cells to elevated glucose (5-25 mmol/l) increased the enzymatic activities of fatty acid synthase 3-fold, acetyl-CoA carboxylase 30-fold, and malic enzyme 1.3-fold. Pyruvate carboxylase and citrate lyase expression remained constant. Similar observations were made at the protein and mRNA levels except for malic enzyme mRNA, which did not vary. Metabolic gene expression changes were associated with chronically elevated levels of citrate, malate, malonyl-CoA, and conversion of glucose carbon into lipids, even in cells that were subsequently exposed to low glucose. Similarly, fatty acid oxidation was suppressed and phospholipid and triglyceride synthesis was enhanced independently of the external glucose concentration in cells preexposed to high glucose. The results suggest that a coordinated induction of glycolytic and lipogenic genes in conjunction with glycogen and triglyceride deposition, as well as increased anaplerosis and altered lipid partitioning, contribute to the adaptive process to hyperglycemia and glucose sensitization of the beta-cell.

Increased fat intake during lactation modifies hypothalamic-pituitary-adrenal responsiveness in developing rat pups: a possible role for leptin.

High fat feeding reportedly enhances hypothalamus-pituitary-adrenal (HPA) responses to stress in adult rats. The present study tested whether elevated fat intake during suckling could have short and/or long lasting consequences on HPA regulation in the offspring. Mothers were fed either a control (C; 5% fat) or high fat (HF; 20% fat) diet during the last week of gestation and throughout lactation. After weaning (day 21), pups from C and HF mothers were fed a chow diet. Offspring from both C- and HF-fed mothers were tested for ACTH and corticosterone responses to stress on postnatal days 10 and 35. We found that HF feeding produced higher lipid levels in the milk of HF compared with C lactating rat dams and that offspring of these mothers had significantly increased retroperitoneal fat pad weight and relative adipose mass on day 21 as well as elevated plasma leptin levels on days 10 and 21 of age. After weaning, pups from the HF mothers had lower plasma leptin levels than those from C mothers. Maternal dietary fat affected HPA responsiveness in the offspring in an age-related manner. Neonatal pups (day 10) from the HF mothers exhibited a reduction in the ACTH and corticosterone responses to ether stress. However, in 35-day-old offspring from HF-fed dams, stress-induced ACTH secretion was increased compared with that in pups from the C-fed mothers. These results demonstrate that maternal diet and increased fat intake through the milk are important regulators of HPA responsiveness in neonates and prepubertal rats. During neonatal life, the blunted stress responsiveness seen with elevated fat intake and the resulting high leptin levels might protect the pups from excessive HPA activation. After removal of the maternal dietary influence and reduced leptin levels, enhanced ACTH stress responses are observed as in adult rats fed a HF diet. Because of the inverse relationship between plasma levels of leptin and HPA responses in pups, the possibility exists that the effects of the HF diet on stress responsiveness are mediated by changes in leptin exposure during development.

The SMN genes are subject to transcriptional regulation during cellular differentiation.

Proximal spinal muscular atrophy (SMA) is an autosomal recessive disease characterized by degeneration of alpha-motor neurons and muscular atrophy. The causal survival motor neuron (SMN) gene maps to a complex region of chromosome 5q13 harbouring an inverted duplication. Thus, there are two SMN genes, SMN1 and SMN2, but SMN1-deficiency alone causes SMA. In this study we demonstrate, for the first time, down-regulation of SMN promoter activity during cellular differentiation. Specifically, the minimal SMN promoter is four times more active in undifferentiated embryonal carcinoma P19 cells compared to cells treated with retinoic acid (RA) to initiate neuronal differentiation. This effect is mediated by sequences contained within the minimal core promoter that we have confined to the 257 nucleotides upstream of exon 1. We have identified seven regions that are highly conserved between the mouse and human SMN core promoters and this region contains the consensus sequence for a number of transcription factors. Most notably, AhR, HNF-3 and N-Oct3 have already been shown to respond to RA treatment of EC cells, while E47, HNF-3, MAZ, N-Oct3 and Pit-1a have been implicated in embryonic, muscle or neural development. In addition, we have mapped two strong transcription initiation sites upstream of SMN exon 1. The novel -79 site identified in this study is preferentially utilized during human foetal development. Furthermore, analysis of RNA from SMA patients with deletions of the entire SMN1 gene or chimpanzees that lack SMN2 suggests that the level of transcription initiation at these sites may be different for the SMN1 and SMN2 genes. Taken together, this work provides the first demonstration of transcriptional regulation of these genes during cellular differentiation and development. Deciphering the underlying mechanisms responsible for regulating SMN transcription may provide important clues towards enhancing SMN2 gene expression, one target for the treatment of SMA.

The energy expenditure of Iranian agricultural workers.

The energy cost of agricultural and standard activities and the daily energy expenditure of male agricultural workers were measured during different seasons in Iranian villages to assess the validity of past and present Food and Agricultural Organization recommended energy allowances for that population. Studies included low income farmers in a village representative of those around the central desert where harvesting takes place under conditions of extreme summer heat. Measurements were also made during the Moslem fasting period when no food may be eaten between dawn and dusk. Energy cost of typical activities was measured by indirect calorimetry using the Max-Planck respirometer and daily energy expenditure was assessed using these figures combined with a diary of activities throughout the 24-hr period. Results of individual activity values are compared with other published figures. Comparison of daily energy expenditure of fasting subjects and nonfasting after Ramazan showed no significant difference. No significant difference was found between values of standardized activities at high summer temperatures and moderate temperatures. Mean values of daily energy expenditure during winter when activity is low are around 2600 kcal/day and for the other seasons of high activity 3400 kcal/day. These figures suggest that past and present Food and Agricultural Organization standards are low for this population.

Questioning riboflavin recommendations on the basis of a survey in China.

Riboflavin status was surveyed in adults aged 35-64 y in 65 counties (two communes per county) in the People's Republic of China by erythrocyte glutathione reductase activity coefficients (EGRACs), by urinary excretion of riboflavin 4 h after the oral administration of 5 mg riboflavin (one commune per county), and by direct measurement of food intake over a 3-d period (one commune per county). EGRAC data were highly correlated between sexes (p less than 0.001) and between neighboring communes within the same county (p less than 0.001) and with riboflavin intake (p less than 0.001). The urinary-riboflavin-load test data were not correlated either with EGRAC or with riboflavin intake. Approximately 90% of the survey subjects were found to be deficient by Western and Chinese reference standards and allowances. Upon reconsideration of the Western experimental data originally used to establish these recommendations, it is suggested that riboflavin allowances are set too high both in China and in Western countries.

The energy expenditure of female carpet weavers and rural women in Iran.

The energy cost of individual activities and the daily energy expenditure of female carpet weavers and villagers were measured in Iranian villages and in the town of Isfahan as part of a series of studies to assess the validity for the population of past and present FAO recommended energy allowances. The energy cost of typical activities was measured by indirect calorimetry using Max-Planck respirometers. Daily energy expenditure was assessed using these figures combined with a 24-hr activity diary. The results of standard activity values are compared with other published values for Europeans and populations of countries with hot climates. The mean daily energy expenditure for both groups was in the order of 2000 kcal/day, below but close to the FAO recommendations which appear valid for rural women in a large part of the country but are probably an underestimate for areas where the participation of women in agriculture is greater.

A combined PET/CT scanner for clinical oncology.

UNLABELLED: The availability of accurately aligned, whole-body anatomical (CT) and functional (PET) images could have a significant impact on diagnosing and staging malignant disease and on identifying and localizing metastases. Computer algorithms to align CT and PET images acquired on different scanners are generally successful for the brain, whereas image alignment in other regions of the body is more problematic. METHODS: A combined PET/CT tomograph with the unique capability of acquiring accurately aligned functional and anatomical images for any part of the human body has been designed and built. The PET/CT scanner was developed as a combination of a Siemens Somatom AR.SP spiral CT and a partial-ring, rotating ECAT ART PET scanner. All components are mounted on a common rotational support within a single gantry. The PET and CT components can be operated either separately, or in combined mode. In combined mode, the CT images are used to correct the PET data for scatter and attenuation. Fully quantitative whole-body images are obtained for an axial extent of 100 cm in an imaging time of less than 1 h. When operated in PET mode alone, transmission scans are acquired with dual 137Cs sources. RESULTS: The scanner is fully operational and the combined device has been operated successfully in a clinical environment. Over 110 patients have been imaged, covering a range of different cancers, including lung, esophageal, head and neck, melanoma, lymphoma, pancreas, and renal cell. The aligned PET and CT images are used both for diagnosing and staging disease and for evaluating response to therapy. We report the first performance measurements from the scanner and present some illustrative clinical studies acquired in cancer patients. CONCLUSION: A combined PET and CT scanner is a practical and effective approach to acquiring co-registered anatomical and functional images in a single scanning session.

Characterization and amino acid sequence of IRT-4, a novel TEM-type enzyme with a decreased susceptibility to beta-lactamase inhibitors.

The clinical isolate Escherichia coli PEY was highly resistant to amoxycillin, ticarcillin and piperacillin associated to beta-lactamase inhibitors such as clavulanic acid, sulbactam, tazobactam and brobactam but susceptible to cephalosporins, aztreonam and imipenem. The susceptibility to mecillinam indicated that this phenotype was not related to hyperproduction of the TEM-1 beta-lactamase. E. coli PEY produced a new plasmid-mediated inhibitor-resistant beta-lactamase of pI 5.2, which was named IRT-4. The determination of the amino acid sequence (Swiss-Prot accession number, P00810) of the purified protein indicated that IRT-4 differed from TEM-1 by two substitutions: Leu for Met-69 (ABL numbering) and Asp for Asn-276. A Met-69-Leu variant of TEM-1, obtained by site-directed mutagenesis, has been described as resistant to clavulanate. The Asp for Asn-276 substitution has not been reported previously. The side chains of Asp-276 and Arg-244 were expected to interact. Determinations of 50% inhibitory concentrations of beta-lactamase inhibitors and substrate profile of IRT-4 suggested that such an ionic bond was implicated in the alteration of the mechanistic process of TEM-1 beta-lactamase.

Energy expenditure over 24 hours, thermal comfort and fat-free mass in Asian men.

Energy expenditure while sitting or sleeping was measured over 24 h in eight young Asian immigrants to France by a suit calorimeter and also by continuous measurement of respiratory gas exchange. Fat-free mass (FFM) was estimated from skinfold measurements. The energy intake per kilogram FFM of the Asians was similar to a group of well-off North Americans of larger body size but similar body composition who had been the subjects of an earlier study. In both groups thermoneutrality was controlled by adjusting the circulating water temperature of the suit calorimeter according to the subjects' preferences. The hourly energy expenditure/kg FFM was 1.2 kcal during sleep and 1.7 kcal while sitting. The mean energy expenditure/kg FFM during a quiet day was 37 kcal/d or 1.5 kcal/h. Using published equations, the estimated BMR was 1490 kcal (6.2 MJ). This estimated value agrees quite well with the BMRs of these subjects as previously determined. In the metabolic room the daily sedentary energy expenditure averaged 1.15 BMR and the energy intake averaged 1.26 BMR for the study subjects in free-living conditions in an urban environment. This is below the 1.4 X BMR currently recommended as a 'minimum' energy intake for subjects of low activity.

Impact of large-dose vitamin A supplementation on childhood diarrhoea, respiratory disease and growth.

One hundred and seventy-two 0.5-3.0-year-old children in a mountainous area of northern Hebei Province of China were randomly assigned to a vitamin A supplementation group (n = 98) or a control group (n = 74) for a 1 year double-blind study. Capsules containing 200,000 IU vitamin A and 40 IU vitamin E were given to the children in the experimental group 3 and 9 months after baseline examination. During the 12 month study period, there was a significant reduction in the incidence of diarrhoea (P < 0.01) and respiratory disease (P < 0.01) in the children of the experimental group compared to the control. Risk of diarrhoea and respiratory disease were respectively 2.5 and 3.4 times higher in the control children. Serum retinol and IgA levels of the treatment group were significantly higher than that of control group (P < 0.01) 7 weeks after first supplementation. There was no significant difference in saliva IgA level between groups. No significant differences in growth were observed. It was concluded that supplementation with large doses of vitamin A decreased the incidence and severity of diarrhoea and respiratory disease in these children, possibly through enhanced activity of the immune system, but had no effect on growth over 1 year.

Urinary riboflavin excretion after a load test in rural China as a measure of possible riboflavin deficiency.

Urinary excretion of riboflavin was measured in 3318 adults 4 h after an oral dose of riboflavin. Male and female subjects aged 35-64 years were selected from 65 mostly rural counties located in 24 provinces of China. Counties were selected to represent a range of seven of the most prevalent cancer mortality rates in China and within counties households were selected at random. Urinary riboflavin excretion levels after a load test, erythrocyte glutathione reductase activity coefficients (EGR-AC), dietary riboflavin intakes, and a large number of other biochemical, dietary, and environmental parameters were measured. Mean dietary intake of riboflavin was 75 per cent of the Chinese recommended dietary allowances (CRDA). Mean meat intake per reference man was very low (26.4 +/- 23.7 g/d) in comparison to Western standards and milk was not consumed at all in most counties. Mean EGR activity coefficients measured on 'blood pools' for both males (1.47 +/- 0.14) and females (1.48 +/- 0.16) indicated that more than two-thirds of the population surveyed was in the medium or high risk category of riboflavin deficiency. Using current reference standards of less than 1.4 mg for 4-h urinary excretion of riboflavin after a 5 mg load, more than 70 per cent of the individuals examined exhibited low levels usually associated with high risk of riboflavin deficiency. In view of the lack of specificity for clinical indications of riboflavin deficiency and the tentative validity of the present CRDA, the interpretation of the data is problematic. We suggest that the present CRDA for this vitamin is set too high and requires critical review and possibly some revision.

The nutrition and health impact of cash cropping in west Africa: a historical perspective.

The impact of cash cropping in West Africa cannot be isolated from its social and historical background. Among the many changes brought to West African economies by cash cropping since the beginning of the century, the present document shows how the extension of trade with European merchants and colonizers created new sets of values and criteria for wealth. Food crops gradually lost their prominent cultural and economics roles to the benefit of export crops or goods. Traditional systems of agricultural production were profoundly disrupted by military actions. They imposed colonial rule and control of trade of tropical crops and goods. Forced labor and compulsory (poorly paid) work assignments were instituted for private and public enterprises: construction of roads, railways, public buildings and plantations. The main justification was the need for cheap labor to cultivate, transport and build roads for the extraction of raw materials. This in turn caused massive migrations from countries such as Burkina Faso (Upper Volta) to Ivory Coast. Cash cropping made systematic collection of taxes possible. An imposition on a per capita basis became the rule and the major incentive of small farmers to engage in commercial farming. Cash cropping made also possible extensive monetarization of West Africa. This results in both favorable and unfavorable effects on the quality of the diet. In profoundly disrupted traditional societies, the diffusion of new consumption patterns was easier and faster. It led to massive food imports of wheat, rice, sugar, alcohol, etc. Cash cropping was (and still is) practiced as a 'mining' agriculture, exhausting soils and deteriorating their fertility for extended periods of time. In the Sudanian and Sahelian zones cash cropping conflicted with the cultivation of grains because peak demands for labor were similar. Therefore, millet and sorghum production declined. Cash cropping was developed in response to the need of European economies for tropical products. However, colonization as a tool to obtain these raw materials was highly inefficient and associated with a considerable misuse of public funds. Together with cash cropping extension was created a network of intermediaries of large European corporations and shopkeepers who would efficiently drain all the earnings from cash cropping away from productive agricultural investments. It made possible the birth of local bourgeoisies and states dedicated almost exclusively to the extraction of a surplus value from the peasantry through cash cropping. It led to a displacement of the role of women; by attributing to them the less profitable food crops, the new production system managed to feed local cities and migrant workers at low cost. Cash cropping provides indirectly a new mean of exploiting women's labor.(ABSTRACT TRUNCATED AT 400 WORDS)

[Fatal acute cerebral edema in a diabetic child]. / Oedème cérébral aigu mortel chez un enfant diabétique.

A case is reported of fatal acute cerebral oedema occurring in a 15-year-old child suffering diabetic ketoacidosis. He had severe gastro-enteritis, with a weight lose of 8 kg over a period of 8 days (initial weight = 50 kg). He was admitted in a stupor with pH 7.15, 129 mmol.l-1 natraemia, and 31 mmol.l-1 blood glucose concentration. Blood osmolaity was calculated to be 310 mosmol.l-1. He was rehydrated with 416 ml.h-1 normal saline and 416 ml.h-1 of 1.4% sodium bicarbonate. At the same time a total dose of 75 i.u. of ordinary insulin was given. After 2 h, the patient's condition suddenly worsened with unreactive coma, bilateral fixed mydriasis, respiratory pauses, and impairment of haemodynamic state (heart rate 150 b.min-1, blood pressure 80/50 mmHg). The diagnosis of cerebral oedema with severe intracranial hypertension was confirmed by different investigations. Despite ventilatory support and continued intensive care, the patient died a few hours later. It is concluded that some degree of subclinical brain swelling could be common occurrence during diabetic ketoacidosis, present maybe even before the start of treatment. Such cases of cerebral oedema are often reported, but the pathophysiological mechanisms remain unclear. However, unlike this case, rehydration must be moderate (less than 41.m-2.day-1), especially in case of hyponatraemia. Insulin and sodium bicarbonate must be used with care. Early rigorous clinical and biological monitoring is essential. Treatment should aim at a progressive correction of the metabolic disturbances.