Quantifying differences in iron deficiency-attributable anemia during pregnancy and postpartum.

Pregnant women in resource-limited settings are highly susceptible to anemia and iron deficiency, but the etiology of postpartum anemia remains poorly defined. To inform the optimal timing for anemia interventions, changes in iron deficiency-attributable anemia through pregnancy and postpartum need to be understood. In 699 pregnant Papua New Guinean women attending their first antenatal care appointment and following up at birth and 6 and 12 months postpartum, we undertake logistic mixed-effects modeling to determine the effect of iron deficiency on anemia and population attributable fractions, calculated from odds ratios, to quantify the contribution of iron deficiency to anemia. Anemia is highly prevalent during pregnancy and 12 months postpartum, with iron deficiency increasing the odds of anemia during pregnancy and, to a lesser extent, postpartum. Iron deficiency accounts for ≥72% of anemia during pregnancy and 20%-37% postpartum. Early iron supplementation during and between pregnancies could break the cycle of chronic anemia in women of reproductive age.

Low knowledge of newborn danger signs among pregnant women in Papua New Guinea and implications for health seeking behaviour in early infancy - findings from a longitudinal study.

BACKGROUND: Globally, 2.5 million babies die in the first 28 days of life each year with most of these deaths occurring in low- and middle-income countries. Early recognition of newborn danger signs is important in prompting timely care seeking behaviour. Little is known about women's knowledge of newborn danger signs in Papua New Guinea. This study aims to assess this knowledge gap among a cohort of women in East New Britain Province. METHODS: This study assessed knowledge of newborn danger signs (as defined by the World Health Organization) at three time points from a prospective cohort study of women in East New Britain Province, factors associated with knowledge of danger signs after childbirth were assessed using logistic regression. This study includes quantitative and qualitative interview data from 699 pregnant women enrolled at their first antenatal clinic visit, followed up after childbirth (n = 638) and again at one-month post-partum (n = 599). RESULTS: Knowledge of newborn danger signs was very low. Among the 638 women, only 9.4% knew three newborn danger signs after childbirth and only one knew all four essential danger signs defined by Johns Hopkins University 'Birth Preparedness and Complication Readiness' Index. Higher knowledge scores were associated with higher gravidity, income level, partner involvement in antenatal care, and education. CONCLUSION: Low levels of knowledge of newborn danger signs among pregnant women are a potential obstacle to timely care-seeking in rural Papua New Guinea. Antenatal and postnatal education, and policies that support enhanced education and decision-making powers for women and their families, are urgently needed.

Collagenous gastritis: Epidemiology and clinical associations.

BACKGROUND: the rare occurrence of collagenous gastritis (CG) makes its epidemiology difficult to investigate. We designed a study to determine the demographic and clinical characteristics as well as the associations of CG with other upper gastrointestinal diseases in a large national clinicopathological database. METHODS: from the IDEA database we extracted all patients with histopathologically documented CG and, in a case-control study, we compared 168 subjects with and 1,286,165 subjects without CG using odds ratios (OR) with their 95% confidence intervals (CI). RESULTS: the prevalence of CG was 13 per 100,000 EGDs. CG was significantly more common among female than male patients (OR: 1.69, 95% CI: 1.20-2.39) and was characterized by a bi-modal age distribution (first peak in patients aged 10-19, second peak primarily in females aged >60 years). CG patients presented with diarrhea (18%), anemia (12%), weight loss (11%), and vomiting (10%). CG was significantly associated with other lymphocytic disorders of the upper gastrointestinal tract, including celiac sprue (2.12, 1.55-2.88), duodenal intraepithelial lymphocytosis (3.71, 2.30-5.98), and lymphocytic gastritis (23.2, 10.9-49.5). CG persisted in 69% of patients who underwent multiple consecutive endoscopies. CONCLUSIONS: the epidemiologic features of collagenous gastritis reflect on different etiologies contributing to its occurrence in children and adults.

Strengthening routine immunization in Papua New Guinea: a cross-sectional provincial assessment of front-line services.

BACKGROUND: Routine immunization programs face many challenges in settings such as Papua New Guinea with dispersed rural populations, rugged geography and limited resources for transport and health. Low routine coverage contributes to disease outbreaks such as measles and the polio that re-appeared in 2018. We report on an in-depth local assessment that aimed to document immunization service provision so as to review a new national strategy, and consider how routine immunization could be better strengthened. METHODS: In East New Britain Province, over 2016 and 17, we carried out a cross-sectional assessment of 12 rural health facilities, staff and clients. The study was timed to follow implementation of a new national strategy for strengthening routine immunization. We used interview, structured observation, and records review, informed by theory-based evaluation, a World Health Organization quality checklist, and other health services research tools. RESULTS: We documented strengths and weaknesses across six categories of program performance relevant to national immunization strategy and global standards. We found an immunization service with an operational level of staff, equipment and procedures in place; but one that could reach only half to two thirds of its target population. Stronger routine services require improvement in: understanding of population catchments, tracking the unvaccinated, reach and efficiency of outreach visits, staff knowledge of vaccination at birth and beyond the first year of life, handling of multi-dose vials, and engagement of community members. Many local suggestions to enhance national plans, included more reliable on-demand services, integration of other family health services and increased involvement of men. CONCLUSIONS: The national strategy addresses most local gaps, but implementation and resourcing requires greater commitment. Long-term strengthening requires a major increase in centrally-allocated resources, however there are immediate locally feasible steps within current resources that could boost coverage and quality of routine immunization especially through better population-based local planning, and stronger community engagement. Our results also suggest areas where vaccination campaigns in PNG can contribute to routine immunization services.

Helicobacter pylori gastritis in HIV-infected patients: a review.

BACKGROUND: The risk factors for acquiring Helicobacter pylori and Human Immunodeficiency Virus (HIV) infections are different: H. pylori is transmitted by gastro- or fecal-oral routes and is associated with low socioeconomic conditions, while HIV is transmitted through sexual intercourse, infected body fluids, and transplacentally. If the host responses to these infections were independent, the prevalence of H. pylori should be similar in HIV-infected and non-infected patients. Yet, several studies have detected a lower prevalence of H. pylori in patients with HIV infection, whereas other studies found either no differences or greater rates of H. pylori infection in HIV-positive subjects. OBJECTIVE: To review studies that addressed the issue of these two simultaneous infections and attempt to determine whether reliable conclusions can be drawn from this corpus of often contrasting evidence. METHODS: Electronic literature search for relevant publications, followed by manual search of additional citations from extracted articles. RESULTS: The initial search yielded 44 publications; after excluding case reports, reviews, narrowly focused articles, and duplicate reports, there remained 29 articles, which are the corpus of this review. With one exception, all studies reported higher rates of H. pylori infection in HIV-negative subjects. Five studies also examined the CD4 lymphocyte counts and found an inverse correlation between the degree of immunosuppression and the prevalence of active H. pylori infection. CONCLUSIONS: Current evidence suggests that it is likely that H. pylori needs a functional immune system to successfully and persistently colonize the human gastric mucosa.

Neuroendocrine proliferations of the stomach: a pragmatic approach for the perplexed pathologist.

The classifications of neuroendocrine proliferations that lead from enterochromaffin-like cell hyperplasia to neuroendocrine tumors in the stomach are complicated and relatively inaccessible to nonspecialists. Consequently, these lesions tend to remain widely underdiagnosed until they progress to easily recognizable neuroendocrine tumors. This review provides simple, yet rigorous guidelines on how to recognize, classify, and diagnose the neuroendocrine proliferations found in the stomach, emphasizing the most common background in which they arise, atrophic gastritis. After a succinct outline of the types and distribution of the neuroendocrine cells in the normal gastric mucosa we discuss the most common situations in which the pathologist needs to think about gastric neuroendocrine cells. In general practice gastric biopsy specimens are often numerically and topographically inadequate for the evaluation of atrophic gastritis; therefore, we have included an algorithm to address specifically the steps that should be taken when confronted with suboptimal sampling. Finally, we illustrate the suggested diagnostic process with 4 cases that are fairly representative of the type of situations encountered in everyday practice. The pathologist who follows our simple steps will be better aware of this neglected area of gastric pathology and will learn to suspect, recognize, and accurately diagnose the most common abnormalities of the neuroendocrine system in the stomach.

Rapid Isocratic Liquid Chromatographic Separation and Quantification of Tryptophan and Six kynurenine Metabolites in Biological Samples with Ultraviolet and Fluorimetric Detection.

A simple, rapid isocratic liquid chromatographic procedure with ultraviolet and fluorimetric detection is described for the separation and quantification of L-tryptophan (Trp) and six of its kynurenine metabolites (kynurenine, 3-hydroxykynurenine, and 3-hydroxyanthranilic, kynurenic, xanthurenic and anthranilic acids). Using the Perkin Elmer LC 200 system, a reverse phase Synergi 4 µ fusion-RP80 A column (250 × 4.6 mm) (Phenomenex), and a mobile phase of 10 mM sodium dihydrogen phosphate: methanol (73:27, by vol) at pH 2.8 and a flow rate of 1.0-1.2 ml/min at 37 °C, a run took ∼13 min. The run took <7 min at 40 °C and a 1.4 ml/min flow rate. Limits of detection of all 7 analytes were 5-72 nM and their recoveries from human plasma and rat serum and liver varied between 62% and 111%. This simple method is suitable for high throughput work and can be further developed to include quinolinic acid and other Trp metabolites.

Low-alcohol beers: contribution to blood-ethanol concentration and its elevation above the UK legal limit after 'topping-up'.

AIMS: The aim of this study was to establish the contribution of low-alcohol beers to blood-ethanol concentration (BEC) and to test if 'topping-up' with these beverages can increase BEC above the 80 mg/dl UK legal limit. METHODS: Healthy male and female volunteers received a dose of ethanol designed to give a BEC of just below 80 mg/dl, and then received one pint (600 ml) of a 1% v/v alcohol beer in the fasting state or after lunch, or of a zero-alcohol or a 0.5% v/v alcohol beer after fasting. BEC was determined enzymatically and data were subjected to ANOVA. RESULTS: Topping-up with a pint of a 1% v/v alcohol beer increased BEC >80 mg/dl in fasting subjects, contributing an extra 12-17 mg/dl, which lasted longer in males (80 min) than in females (20 min). A 0.5% v/v alcohol beer increased BEC above 80 mg/dl only in males, which lasted for 60 min. After food intake, the 1% v/v alcohol beer increased BEC above 80 mg/dl transiently only in males. CONCLUSIONS: Low-alcohol beers make a significant contribution to blood-ethanol concentration and can increase it above the UK legal limit. Their use as a 'top-up' should be discouraged. Low-alcohol beers have a place as a substitute for normal-strength beverages as a strategy for decreasing alcohol consumption in general and in countries where low legal alcohol limits are in force or being contemplated.

Comparison of 50- and 100-g L -tryptophan depletion and loading formulations for altering 5-HT synthesis: pharmacokinetics, side effects, and mood states.

RATIONALE: Differences in 5-hydroxytryptamine (5-HT) function have been the subject of extensive research in psychiatric studies. Many studies have manipulated L -tryptophan (Trp) levels to temporarily decrease (depletion) or increase (loading) 5-HT synthesis. While most researchers have used a 100-g formulation, there has been ongoing interest in using smaller-sized formulations. OBJECTIVES: This study examined the time course of multiple plasma indicators of brain 5-HT synthesis after a 50-g depletion and loading as a comparison to the corresponding 100-g formulations that are typically used. MATERIALS AND METHODS: Plasma was collected from 112 healthy adults at seven hourly intervals after consumption of either a 50- or 100-g depletion or loading. Self-ratings of mood and somatic symptoms were completed before and after Trp manipulations. RESULTS: The primary findings were that (1) the 50- and 100-g formulations produced the expected changes in plasma indicators after both depletion (-89% and -96%, respectively) and loading (+570% and +372%, respectively); (2) the 100-g depletion showed more robust effects at the 4, 5, and 6 h measurements than the 50-g depletion; (3) there was significant attrition after both the 100-g depletion and loading, but not after either of the 50-g formulations; and (4) both the 50- and 100-g depletions produced increases in negative self-ratings of mood and somatic symptoms, while loading significantly increased negative ratings after the 100 g only. CONCLUSIONS: There are important considerations when choosing among formulation sizes for use in Trp manipulation studies, and the complete 7-h time-course data set of the typical plasma Trp measures presented here may help researchers decide which methodology best suits their needs.

Heterogeneity of serum tryptophan concentration and availability to the brain in patients with the chronic fatigue syndrome.

We assessed the serotonin status of patients with the chronic fatigue syndrome (CFS). Tryptophan (Trp) availability to the brain, expressed as the ratio of concentration of serum Trp to the sum of those of its five competitors (CAA), and other parameters of Trp disposition were compared in 23 patients with the CFS and 42 healthy controls. The serum [free Trp]/[CAA] ratio was 43% higher in CFS patients, due to a 48% higher [free Trp]. [Total Trp] was also significantly higher (by 19%) in CFS patients, and, although the [total Trp]/[CAA] ratio did not differ significantly between the control and patient groups, the difference became significant when the results were co-varied with age and gender. [CAA] was not significantly different between groups, but was significantly lower in females, compared to males, of the CFS patient group. We have established normal ranges for Trp disposition parameters and propose criteria for defining the serotonin-biosynthetic status in humans. We have provisionally identified two subgroups of CFS patients, one with normal serotonin and the other with a high serotonin status. The relevance of our findings to, and their implications for, the pharmacological and other therapies of the chronic fatigue syndrome are discussed.

An evolving model for training and education in resource-poor settings: teaching health workers to fish.

Training and education of health workers remains an indispensable part of good health development in resource-poor settings. Many past training programs have failed to achieve significant gains in health outcomes because of poor selection of participants, inadequate methodology, and/or the influence of external factors in the health system or social environment. The solutions lie in better planning of "who" and "what" should be trained; effective methods based on adult learning principles; alternative methods that maximise learner input and locate training as close as possible to the workplace and its problems; appropriate inclusion of the community; and coordination with other health system interventions.

Sensorimotor gating effects produced by repeated dopamine agonists in a paradigm favoring environmental conditioning.

RATIONALE: It is not known whether dopamine agonist-induced disruption of prepulse inhibition (PPI) can be conditioned to the environment, a phenomenon established for dopamine agonist-induced locomotor activation and other behaviors. Furthermore, the literature is contradictory regarding whether PPI disruption, like locomotor activity, can become sensitized after repeated dopamine agonist administration. Differences in methodology (e.g. drug-environment pairing) may have contributed to these contradictory findings. OBJECTIVES: In a series of studies, we investigated whether dopamine agonist-induced disruption of PPI could be conditioned and whether repeated administration of dopamine agonists, in a paradigm favorable to conditioning, would produce sensitization to dopamine agonist-induced disruption of PPI. METHODS: One group of rats were administered subcutaneous apomorphine (0.5 mg/kg) daily for 7 (experiment 1) or 5 (experiment 3) consecutive days contingent with startle testing (in testing rooms, immediately before test sessions). A second group received the same apomorphine dose daily in a manner non-contingent with behavioral testing (in home cages after test sessions). The following day, all rats received vehicle injections contingent with the test environment to assess for environmental conditioning (vehicle challenge day). The next day, all animals received a challenge of apomorphine (0.5 mg/kg) contingent with the test environment to assess the contribution of drug-environment pairing on changes observed in apomorphine-induced disruption of PPI (apmorphine challenge day). PPI was measured immediately after drug injections in the test environment. A separate study (experiment 2) tested amphetamine (3.0 mg/kg) using a similar methodology. In a fourth study, rats were pretreated with haloperidol (1.0 mg/kg) or saline prior to receiving daily apomorphine to see if haloperidol could modify the changes in PPI produced by repeated apomorphine administration. RESULTS: On the vehicle challenge day, PPI exhibited by the rats that received daily apomorphine contingent with the testing environment did not differ from the group that received vehicle contingent with the testing environment. However, animals receiving apomorphine contingent with testing exhibited partial tolerance to its PPI effects during the conditioning period. The PPI exhibited by both groups did not differ significantly on the apomorphine-challenge day. Amphetamine produced a complete tolerance to its PPI effects by day 3. Haloperidol pretreatment blocked the PPI tolerance produced by repeated apomorphine injections. CONCLUSIONS: These results suggest: 1) unlike locomotion, PPI disruption induced by apomorphine cannot be conditioned to the environment; 2) unlike locomotion, repeated adminstration of dopamine agonists produce tolerance, rather than sensitization, to PPI; 3) environmental factors do not seem to be critical for PPI tolerance; and 4) dopamine receptors mediate PPI tolerance to apomorphine.