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Biomedical subjects

P Arthur

Publications and source records attributed to P Arthur.

At least 19 recordsLinked to original sources
PubMed2006

The mitotic manipulation of cytotrophoblast differentiation in vitro.

The placental syncytiotrophoblast is of paramount importance in optimising feto-maternal interactions. Syncytiotrophoblast is generated by the differentiation and fusion of underlying cytotrophoblasts. This process is aberrant in complicated pregnancies. We hypothesized that cell cycle withdrawal determines the phenotypic decision-making of cytotrophoblasts. We therefore investigated the effects of broad-spectrum mitotic inhibitors on cytotrophoblast differentiation. Villous tissue was dissected from term placentae of normal pregnancies and cultured on Netwell supports. Over 48 h, the original syncytiotrophoblast was detached and underlying cytotrophoblasts exposed. The resulting villi were treated with mitotic blockers (Ara-C, colcemid, cyclohexamide, doxorubicin hydrochloride, hydroxyurea, L-Mimosine, purvalanol A). The media was recovered and analysed for lactacte dehydrogenase (LDH) and human chorionic gondadotrophin (hCG), markers of tissue viability and cytotrophoblast differentiation, respectively. The resulting tissue was processed for proliferative activity thorough Ki-67 immunorecognition. Colcemid, cyclohexamide, hydroxyurea, and purvalanol A showed significant cytotoxicity over 48 h incubation. Villous tissue exposed to 0.01 mM and 0.1mM Ara-C, doxorubicin hydrochloride and L-Mimosine showed no increase in liberated LDH. hCG production increased exponentially with cytotrophoblast differentiation. Higher concentrations of Ara-C and L-Mimosine significantly encouraged hCG production. In addition, total cell and cytotrophoblast proliferation were reduced with Ara-C and L-Mimosine treatment. The inhibition of DNA synthesis and replication with Ara-C and L-Mimosine suppressed active proliferation of villus components and exaggerated the biochemical differentiation of cytotrophoblasts. Cell cycle disruption is therefore a basic trigger for cytotrophoblast differentiation. This approach provides a mechanism for encouraging syncytiotrophoblast formation and may hold benefits for conditions where syncytiotrophoblast cover is attenuated.

Cycloheximide↗
PubMed2006

Vitamin A supplementation increases ratios of proinflammatory to anti-inflammatory cytokine responses in pregnancy and lactation.

Vitamin A supplementation reduces child mortality in populations at risk of vitamin A deficiency and may also reduce maternal mortality. One possible explanation for this is that vitamin A deficiency is associated with altered immune function and cytokine dysregulation. Vitamin A deficiency in pregnancy may thus compound the pregnancy-associated bias of cellular immune responses towards Th-2-like responses and exacerbate susceptibility to intracellular pathogens. We assessed mitogen and antigen-induced cytokine responses during pregnancy and lactation in Ghanaian primigravidae receiving either vitamin A supplementation or placebo. This was a double-blind, randomized, placebo-controlled trial of weekly vitamin A supplementation in pregnant and lactating women. Pregnancy compared to postpartum was associated with a suppression of cytokine responses, in particular of the proinflammatory cytokines interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha. Mitogen-induced TNF-alpha responses were associated with a decreased risk of peripheral parasitaemia during pregnancy. Furthermore, vitamin A supplementation was significantly associated with an increased ratio of mitogen-induced proinflammatory cytokine (IFN-gamma) to anti-inflammatory cytokine (IL-10) during pregnancy and in the postpartum period. The results of this study indicate that suppression of proinflammatory type 1 immune responses and hence immunity to intracellular infections, resulting from the combined effects of pregnancy and vitamin A deficiency, might be ameliorated by vitamin A supplementation.

Cytokines↗
PubMed2002

Prolonged childhood Cushing's syndrome secondary to intralesional triamcinolone acetonide.

Intralesional corticosteroids have been used in the treatment of hypertrophic keloid scars for over 40 years. The few complications documented have mostly been local skin changes, viz depigmentation and cutaneous atrophy. Cushing's syndrome following intralesional injection is rare and usually self-limiting following cessation of therapy. This report describes a 9-year-old girl who developed Cushing's syndrome 2-3 weeks after a single treatment with 40 mg triamcinolone acetonide injected into keloids. Features of Cushing's syndrome and a suppressed hypothalamic-pituitary axis were present up to 9 months later. Three years after glucocorticoid injections, features of Cushing's syndrome had largely disappeared. Dosages of intralesional steroids normally recommended for adults are inappropriate for children.

Child↗
PubMed2001

Treatment of anemia with microencapsulated ferrous fumarate plus ascorbic acid supplied as sprinkles to complementary (weaning) foods.

BACKGROUND: Standard therapy for anemia in infants is ferrous sulfate drops administered 3 times/d. Adherence to treatment, however, is often poor. One likely reason for poor adherence is the unpleasant side effects associated with drops. OBJECTIVE: The objective was to evaluate the use of a new form of iron and a delivery system to treat anemia in infants that is likely to produce better adherence to treatment. DESIGN: Using a prospective, randomized, controlled design, we studied 557 anemic children aged 6-18 mo (hemoglobin: 70-99 g/L) in rural Ghana. One group received a daily sachet of microencapsulated ferrous fumarate (80 mg elemental Fe) in powder form plus ascorbic acid to be sprinkled onto any complementary food eaten (sprinkles group); a control group received ferrous sulfate drops 3 times/d for 2 mo (total dose: 40 mg elemental Fe). Hemoglobin and serum ferritin concentrations were measured at baseline and at the end of treatment. RESULTS: Successful treatment of anemia (hemoglobin > 100 g/L) occurred in 58% of the sprinkles group and in 56% of the drops group, with minimal side effects in both groups. Geometric mean ferritin concentrations increased significantly in each group from baseline to the end of treatment (P < 0.001). CONCLUSION: Use of ferrous sulfate drops or a single daily dose of microencapsulated ferrous fumarate sprinkles plus ascorbic acid resulted in a similar rate of successful treatment of anemia without side effects. To our knowledge, this is the first demonstration of the use of microencapsulated iron sprinkles to treat anemia. Improved ease of use may favor the use of sprinkles to deliver iron.

Anemia, Iron-Deficiency↗
PubMed2001

Randomized, controlled trial of single versus 3-times-daily ferrous sulfate drops for treatment of anemia.

OBJECTIVE: Adherence to treatment of iron-deficiency anemia often is poor in both developed and developing countries. The current standard therapy is ferrous sulfate drops (or syrup) administered 3 times daily. It is possible that adherence would improve with a single-dose daily treatment regimen. We compared the use of single versus 3-times-daily ferrous sulfate drops, at the same total iron dose, on treatment of anemia in infants. METHODS: To obtain a large enough cohort of anemic subjects, we performed the study in rural Ghana. Using a prospective, randomized, controlled design, we studied 557 anemic children (age range: 6-24 months; hemoglobin values: 70-99 g/L). One group (n = 280) received ferrous sulfate drops once daily (40 mg elemental iron), and the control group (n = 277) received ferrous sulfate drops 3 times per day (total dose, 40 mg elemental iron). Treatment lasted for 2 months. Hemoglobin and serum ferritin values were measured at baseline and at the end of the study. RESULTS: Successful treatment of anemia (hemoglobin >100 g/L) occurred in 61% of the single-dose and in 56% of the 3-times-daily group. Geometric mean ferritin levels increased significantly in each group from baseline to the final visit. Side effects were minimal and similar between the 2 groups. CONCLUSION: A single versus a 3-times-daily dose of ferrous sulfate drops over 2 months resulted in a similar rate of successful treatment of anemia, without side effects. To our knowledge, this is the first demonstration of the use of a single-dose daily regimen to treat anemia. Although not examined in the current study, use of a single-dose daily regimen may improve adherence to treatment of anemia in infants.

Anemia, Iron-Deficiency↗
PubMed2001

Validity of women's self-reported obstetric complications in rural Ghana.

This retrospective study assessed the utility of women's self-reports to identify obstetric complications in rural Ghana. All consenting obstetric and postpartum inpatients, presenting from the seventh month of gestation to 42 days postpartum, were interviewed at the Holy Family Hospital, Techiman and were asked about their signs and symptoms. A combination of clinical examination and laboratory testing of urine and blood samples was used for determining case status. Self-reported obstetric complications of 340 women were compared with the corresponding diagnostic status for their sensitivity, specificity, predictive value, and test-efficiency. Using algorithms that could not be practically applied at the community level, self-reported symptoms correctly identified the majority (75%) of complicated and uncomplicated pregnancies, but missed one-quarter of cases requiring emergency obstetric care. The positive predictive value of 50% indicates that women's self-reported symptoms should not be used in estimating the incidence of these conditions or in identifying women requiring referral in this population.

Algorithms↗
PubMed2001

Diagnostic dilemma in coinfection.

A Fifteen years girl belonging to a low socioeconomic status was admitted with peritonsillar abscess caused by methicillin resistant Staphylococcus aureus (MRSA), high fever, diarrhoea and septicaemic shock. Initial blood cultures and widal test, stool cultures and routine stool examination were non-contributory to the diagnosis. A bone marrow culture in the second week confirmed the diagnosis of Salmonella typhi infection. Examination of a fresh stool sample showed cysts of Entamoeba histolytica. She was treated with ciprofloxacin, metronidazole, augmentin and ceftriaxone. She had no clinical evidence of immunosuppression prior to this episode and her HIV test was negative. This case report highlights the presence of community acquired MRSA infection causing perititonsillar abscess, and the diagnostic dilemma of fever and diarrhoea due to coinfection with Salmonella typhi and Entamobea histolytica.

Adolescent↗
PubMed1999

Differences in fuel utilization between trout and human thrombocytes in physiological media.

Cell culture preparations now play a significant and essential role in physiological and biochemical studies of cell biology. However, the fuels offered in cell culture media are only glucose and glutamine, plus whatever might be in the added sera. It is currently difficult to find a rational way forward on this problem, as there are few data on what fuels cells use in vivo or even in an in vitro physiological situation. A recent study on human platelets redressed the situation somewhat by finding that 75% of ATP turnover could be accounted for by aerobic glycolysis, and by the oxidation of glucose, hydroxybutyrate, acetate, glutamine, palmitate and oleate. In the present study we used a similar strategy to investigate fuel choices by trout thymocytes, cells with a similar function but from a different phylogenetic group. When these cells were presented with a physiological medium, we found that aerobic glycolysis accounted for 9% of total ATP turnover, glucose and glutamine oxidation made a combined contribution of 2.3%, oleate and palmitate oxidation accounted for 15%, and 74% was unaccounted for. These patterns of fuel use are very different from that in human platelets. They demonstrate the cell- and animal-specific nature of cellular metabolism and again expose the inadequacy of the fuel component in culture media.

Adenosine Triphosphate↗
PubMed1999

A mobile screening unit, practicalities and problems.

The need for a mobile screening unit to travel throughout Scotland to measure and modify cardiovascular risk factors in the apparently healthy working population was fulfilled by the conversion of a double-decker bus. The aim of the project was to assess the incidence of risk factors in healthy individuals and to modify their risk factors by individual counselling. Many unforeseen practical problems were encountered and overcome during the planning stage and during the project. The team of specially trained staff spent three and a half years screening more than 20,000 people throughout Scotland. This project provides a model for other screening projects involving a multicentre/scattered cohort.

Adult↗
PubMed1998

The impact of vitamin A supplementation given during a pneumonia episode on the subsequent morbidity of children.

OBJECTIVE: To evaluate the impact of large-dose vitamin A supplementation given to infants > 6 months old (200000 IU) and to preschool children aged 1-4 years (400000 IU) during a pneumonia episode, on their subsequent morbidity and severe morbidity. METHOD: In a randomized, double-blind, placebo controlled trial, the children were followed-up with 2-weekly visits at home for 16 weeks, with the first visit 2 weeks after treatment for pneumonia was initiated. The field workers asked about the presence of morbidity on the day of the visit and in the previous two weeks and about the occurrence and number of clinic attendances and hospital admissions since the last visit. They also measured the patients respiratory rate and temperature and assessed the children for the presence of cyanosis, chest indrawing and wheezing. RESULTS: Except for the prevalence of diet refusal which was higher in the vitamin A group, no differences between the study groups were observed, either in the prevalence of morbidity or in the incidence of clinic attendances and hospital admissions. CONCLUSION: No evidence was found for a beneficial effect of vitamin A given during acute pneumonia on the subsequent morbidity and severe morbidity of children in a population with marginal vitamin A deficiency.

Brazil↗
PubMed1997

Randomised, double blind, placebo controlled clinical trial of efficacy of vitamin A treatment in non-measles childhood pneumonia.

OBJECTIVE: To evaluate the impact on clinical recovery and severity of the addition of large doses of vitamin A to the standard treatment for childhood pneumonia. DESIGN: A randomised, double blind, placebo controlled trial. SETTING: Study children were recruited at a public hospital in Recife, north east Brazil, an area of marginal vitamin A deficiency. SUBJECTS: 472 children aged 6 to 59 months with clinical diagnosis of pneumonia. INTERVENTIONS: 200,000 IU (infants) or 400,000 IU (1-4 year olds) of vitamin A in oil or similar capsules of placebo divided into two daily oral doses, in addition to the standard treatment. MAIN OUTCOME MEASURES: Duration of the episode and incidence of adverse outcomes. RESULTS: The groups were similar with respect to overall duration of pneumonia and incidence of adverse outcomes. Children who received vitamin A, however, were less likely to have fever by day 3 (P = 0.008) and were 29% less likely to fail to respond to the first line antibiotic (P = 0.054). CONCLUSION: There was little evidence for an effect of vitamin A treatment on the immediate outcome of the pneumonia episode.

Child, Preschool↗
PubMed1997

Quantitative modelling of the effects of selected intracellular metabolites on pH in fish white muscle

A model is presented that provides guidelines to the identification of key experimental variables influencing proton balance and intracellular pH in vertebrate white muscle. We have drawn on data from the literature on rainbow trout (Oncorhynchus mykiss) in an attempt to quantify the influence of metabolic, ionic and transport components of proton generation and proton consumption after exercise. Only minor changes in proton balance and in calculated intracellular pH were caused by considering changes in the concentration of bicarbonate or including the acid&shy;base characteristics of purine nucleotides. Intracellular pH, as estimated by the model, was more acidic at some time points in recovery compared with in vivo measurements, and this would appear to result mainly from inaccuracies in quantifying the phosphate component of proton buffering. Nevertheless, the model was able to simulate the typical pattern of muscle acidosis and recovery observed for trout, including the transient post-exercise acidification and the slow recovery rate. As with previous pHi models, comparison of model estimates with experimental observations is essential in this approach in order to identify whether all of the relevant metabolic processes have been considered for accurate quantification of proton balance within the white muscle compartment.

Journal Article↗
PubMed1996

Carbohydrate metabolism in human platelets in a low glucose medium under aerobic conditions.

The metabolism of human platelets has been the subject of investigation for at least three decades, at the level of basic metabolism, and because of the increasing requirement for platelet storage. Platelets are relatively active metabolically and are typical cells in terms of fuels and metabolic pathways. They contain glycogen and utilize glucose and demonstrate aerobic glycolysis and carbohydrate oxidation. Both glycolysis and carbohydrate oxidation contribute significantly to total ATP turnover, so platelets are an ideal system in which to study the partitioning of carbohydrate metabolism between the two available fuels and the two available pathways, in the presence of adequate oxygen. We have designed a system whereby we can study carbohydrate metabolism in relatively pure human platelets, under sterile conditions, over long periods. The system enables us to determine total ATP turnover and, with the aid of a mathematical model, the contribution to this turnover of glycolysis and the oxidation of glucose/glycogen and lactate. When glucose and glycogen are present, most of the glucose and glycogen utilised is converted to lactate, but lactate is being oxidised at this time. When glucose/glycogen stores are exhausted lactate oxidation continues and increases with the result that carbohydrate oxidation accounts for 41% of total ATP turnover over 48 h.

Adenosine Triphosphate↗
PubMed1996

Is prevalence of diarrhea a better predictor of subsequent mortality and weight gain than diarrhea incidence?

A number of different outcome measures have been proposed for use in prospective studies of morbidity associated with childhood diarrhea. These include the number of episodes experienced by each child over a defined period (a measure of incidence) and the number of days of diarrhea divided by the total number of days of observation for each child (a measure denoted "longitudinal prevalence"). The authors examined data from Ghana to determine which of these measures is more strongly associated with weight gain over a 4-month period and subsequent mortality. Both diarrhea incidence and longitudinal prevalence were associated with weight gain in children aged 6-23 months, but a statistically stronger association was observed with longitudinal prevalence (likelihood ratio statistic 28.95 on 1 degree of freedom against 19.70 for incidence). Neither measure was associated with weight gain in younger or older children. Longitudinal prevalence, but not incidence, was strongly associated with subsequent mortality (p = 0.002 for longitudinal prevalence; p = 0.557 for incidence). Although many epidemiologic studies of diarrhea focus on incidence, these data suggest that longitudinal prevalence is more strongly predictive of long-term health outcome. The authors conclude that longitudinal prevalence merits greater attention as a measure of outcome in diarrhea studies.

Child, Preschool↗
PubMed1996

Effect of vitamin A supplementation on the growth of young children in northern Ghana.

The effect of prophylactic vitamin A supplementation on child growth was studies in two randomized, placebo-controlled trials carried out in adjacent areas of northern Ghana between 1989 and 1991. In the Health Study, the midupper arm circumference (MUAC) and weight of the approximately 1500 children (aged 6-59 mo) in the trial were measured every 4 wk for up to 52 wk. In addition, MUAC, weight, and height were measured at each of the four potential vitamin A or placebo dosing times, which were at 4-mo intervals. In the Survival Study, MUAC and weight were measured at 4-mo intervals at each of seven dosing rounds in the approximately 15 000 children currently in the trial. Overall, there were > 90 000 observations of weight and MUAC in > 25 000 children, and 3347 observations of length/height in 1546 children. Within each study, the mean monthly weight, MUAC, and gains in length/height in each treatment group were compared by using multilevel modeling. There were no significant differences in either MUAC or gains in length/height. The only significant difference in weight gain was in the Survival Study: children in the vitamin A-supplemented group who were > or = 36 mo of age had a mean weight gain that was 3 g lower per month (95% CI: 0.4, 5.0, P = 0.02) than that in the placebo group; a difference that was unlikely to be functionally important in this age group. Vitamin A supplementation did not lead to any increased growth in this population of young children, in whom supplementation reduced mortality and severe morbidity substantially.

Anthropometry↗
PubMed1996

The contribution of vitamin A to public health.

Vitamin A deficiency among children in developing countries remains the leading cause of preventable severe visual impairment and blindness, and is a significant contributor to severe infections and death, particularly from diarrhea and measles. Vitamin A deficiency is also likely to increase vulnerability to other illnesses in both women and children, such as iron-deficiency anemia, and may be an important factor contributing to poor maternal performance during pregnancy and lactation and to growth deficits in children. Benefits to public health can be expected by improving the vitamin A status of deficient populations through an appropriate mix of acceptable, affordable, and available programs including promotion of breast-feeding, control of infections, dietary diversification, food fortification, and supplementation. Benefits include not only improved health and welfare for individuals and their families, but also improved chances of survival for an estimated 254 million children.

Anemia, Iron-Deficiency↗
PubMed1995

Vitamin A supplementation and childhood malaria in northern Ghana.

Two companion, randomized, placebo-controlled trials of prophylactic vitamin A supplementation provided the opportunity to assess the impact of supplementation on malaria parasitemia, morbidity, and mortality in young children in northern Ghana. In the mortality study, 21,906 children were visited every 4 mo over 2 y, and in the morbidity study 1455 children were visited weekly for 1 y. There was no difference between children supplemented with vitamin A and those given placebo in malaria mortality rates (rate ratio = 1.03; 95% CI 0.74, 1.43) or fever incidence based on reported symptoms. Malaria parasitemia rates, parasite densities in children with a positive blood smear, and rates of probable malaria illness also did not differ between treatment groups. There was no correlation between serum retinol at the beginning of the trial and subsequent malaria parasitemia in children who received placebo (r = 0.01). It is concluded that vitamin A supplementation had no impact on malaria in this population.

Child↗