Progression of anaemia during antenatal period among South African pregnant women.

Background: Anaemia in pregnancy is a known public health problem in South Africa. Maternal, perinatal morbidity and mortality are known to be associated with anaemia in pregnancy. Very little is known from literature with regards to the progression of anaemia during the antenatal period of pregnancy. Objectives: To estimate haemoglobin levels, the prevalence and determinants of anaemia at different gestational ages and to show the trend. Method: A retrospective cohort (follow-up) study was conducted using the antenatal clinic register. Prevalence rates of anaemia (haemoglobin < 11 g/dl) at different gestational ages were measured. Factors associated with anaemia were assessed using chi-square test and stepwise multivariate logistic regression analysis. Results: A total of 801 pregnant women were enrolled at the booking visit and followed-up during their antenatal period. The prevalence of anaemia at the booking visit was 37%. The prevalence of anaemia at 20, 26, 32 and 36 weeks of gestation were 36.6%, 39.6%, 39.8% and 29.2% respectively. Binary logistic regression at the booking visit showed that teenage women were 2.5 times more likely to have anaemia (OR=2.5, p=0.005) than older women. Women who booked during the first trimester were 60% less likely to have anaemia (OR= 0.40, P=0.005) at the booking visit and 62% less likely to be anaemic at 36 weeks of gestation (OR=0.38, p=0.013) compared to those who booked late for antenatal care. Conclusion: Prevalence of anaemia during pregnancy was high. Early booking for antenatal care was a predictor for lower rate of anaemia. Thus, health education strategy should be encouraged for early antenatal booking.

Progression of anaemia during antenatal period among South African pregnant women

Background: Anaemia in pregnancy is a known public health problem in South Africa. Maternal, perinatal morbidity and mortality are known to be associated with anaemia in pregnancy. Very little is known from literature with regards to the progression of anaemia during the antenatal period of pregnancy. Objectives: To estimate haemoglobin levels, the prevalence and determinants of anaemia at different gestational ages and to show the trend. Method: A retrospective cohort (follow-up) study was conducted using the antenatal clinic register. Prevalence rates of anaemia (haemoglobin < 11 g/dl) at different gestational ages were measured. Factors associated with anaemia were assessed using chisquare test and stepwise multivariate logistic regression analysis. Results: A total of 801 pregnant women were enrolled at the booking visit and followed-up during their antenatal period. The prevalence of anaemia at the booking visit was 37%. The prevalence of anaemia at 20, 26, 32 and 36 weeks of gestation were 36.6%, 39.6%, 39.8% and 29.2% respectively. Binary logistic regression at the booking visit showed that teenage women were 2.5 times more likely to have anaemia (OR=2.5, p=0.005) than older women. Women who booked during the first trimester were 60% less likely to have anaemia (OR= 0.40, P=0.005) at the booking visit and 62% less likely to be anaemic at 36 weeks of gestation (OR=0.38, p=0.013) compared to those who booked late for antenatal care. Conclusion: Prevalence of anaemia during pregnancy was high. Early booking for antenatal care was a predictor for lower rate of anaemia. Thus, health education strategy should be encouraged for early antenatal booking

Correlation of Mean Platelet Volume with ST Segment Resolution after Thrombolytic Therapy in Patients with ST Elevation Myocardial Infarction.

Acute occlusive thrombosis of the coronary artery is the principal cause of myocardial infarction where platelets play an important role. Large size platelets, easily measured by mean platelets volume (MPV) are thrombogenic and commonly seen after ST-segment elevation myocardial infarction (STEMI). ST segment resolution has been shown as a simple non-invasive marker that reflects both epicardial and myocardial reperfusion following thrombolysis. The present study intended to investigate whether MPV on admission correlated with ST segment resolution following thrombolysis in STEMI patient. This cross-sectional analytical study was conducted in the department of cardiology, Mymensingh Medical College and Hospital (MMCH), Mymensingh, Bangladesh from December, 2016 to June, 2018. Total 284 patients with first attack of STEMI were included after considering inclusion and exclusion criteria. Sample population was divided into two groups, Group I - Patients with successful ST segment resolution (≥50%). Group II - Patients with impaired ST segment resolution (<50%). MPV on admission was estimated during estimation of Complete Blood Count (CBC) by Automated Haematology Analyzer & compared between two groups. Successful ST segment resolution (≥50%) was seen in 67% of patients after thrombolysis. Admission MPV was higher in patients with impaired ST segment resolution (<50%) group than patients with ≥50% ST-segment resolution group (12.42±0.89fl vs.10.35±0.77fl respectively, p=0.001). Statistically significant strong negative correlation between MPV and ST segment resolution percentage (r = -0.742, p=0.001) suggesting that the higher the level of MPV, the lower the ST segment resolution percentage in first attack of STEMI patients. Multivariate regression analysis found MPV level on admission as an independent predictor of ST segment resolution. The study concluded that high MPV on admission correlate with impaired ST segment resolution following thrombolysis in STEMI patients.

In utero arsenic exposure is associated with impaired thymic function in newborns possibly via oxidative stress and apoptosis.

Prenatal arsenic exposure is associated with increased infant morbidity and reduced thymus size, indicating arsenic-related developmental immunotoxicity. We aimed to evaluate effects of prenatal arsenic exposure on thymic function at birth and related mechanisms of action. In a Bangladeshi cohort, arsenic was measured in urine (U-As, gestational week (GW) 8 and 30) and blood (B-As, GW14) in 130 women. Child thymic index was measured by sonography at birth and thymic function by signal-joint T-cell receptor-rearrangement excision circles (sjTRECs) in cord blood mononuclear cells (CBMC). In a subsample (n = 44), sjTRECs content in isolated CD4(+) and CD8(+) T cells, expression of oxidative-stress defense and apoptosis-related genes in CBMC, arsenic concentrations (urine, placenta, and cord blood), and oxidative stress markers in placenta and cord blood were measured. In multivariable-adjusted regression, ln U-As (GW8) was inversely associated with ln sjTRECs in CBMC (B = -0.25; 95% confidence interval [CI] -0.48 to -0.01). Using multivariable-adjusted spline regression, ln U-As (GW30) and ln B-As (GW14) were inversely associated with ln sjTRECs in CBMC (B = -0.53; 95% CI -0.93 to -0.13 and B = -1.27; 95% CI -1.89 to -0.66, respectively) below spline knots at U-As 150 µg/l and B-As 6 µg/kg. Similar inverse associations were observed in separated CD4(+) and CD8(+) T cells. Arsenic was positively associated with 8-hydroxy-2'-deoxyguanosine in cord blood (B = 0.097; 95% CI 0.05 to 0.13), which was inversely associated with sjTRECs in CD4(+) and CD8(+) T cells. In conclusion, prenatal arsenic exposure was associated with reduced thymic function, possibly via induction of oxidative stress and apoptosis, suggesting subsequent immunosuppression in childhood.

Arsenic methylation efficiency increases during the first trimester of pregnancy independent of folate status.

Exposure to inorganic arsenic during pregnancy may negatively influence the offspring, though efficient metabolism of arsenic to dimethylarsinic acid (DMA) likely reduces the health risks. This study aimed to evaluate methylation of arsenic over the entire pregnancy and the influence of nutritional status. We studied longitudinally the arsenic metabolite pattern in the urine of 324 pregnant women exposed to arsenic via drinking water and food in rural Bangladesh. Metabolism of arsenic to DMA increased markedly over the course of pregnancy, with the greatest improvement occurring in the first trimester, along with a marked decrease in the most risk-associated monomethylated metabolite. This improvement in methylation was not associated with nutritional status, including vitamin B(12) and folate. Efficient methylation to DMA was associated with improved urinary excretion of arsenic, relative to blood arsenic concentrations, indicating that micronutrient-independent up-regulation of arsenic metabolism already in early pregnancy may provide protection for the fetus.

Accumulation of cadmium in human placenta interacts with the transport of micronutrients to the fetus.

Cadmium (Cd) is a widespread, highly toxic environmental pollutant known to accumulate in human placenta. The aim of the present study was to elucidate to what extent the accumulation of Cd in human placenta interacts with the transport of micronutrients to the fetus. Cd and micronutrients were measured in placenta and umbilical cord blood from 44 non-smoking, rural Bangladeshi women, using ICPMS. Metallothionein (MT) protein expression was determined in placenta using Western blot. Cd in placenta (median 110 microg/kg dry weight, 20 microg/kg wet weight) was positively associated with maternal urinary Cd. It was also positively associated with Cd in umbilical cord blood (median 0.16 microg/kg), but negatively associated with zinc (Zn; median 3mg/kg) in umbilical cord blood. Umbilical cord blood Zn was positively associated with birth anthropometry measures, and the Cd-related impairment of Zn in umbilical cord blood seemed to decrease size at birth. In multivariate analysis, MT protein expression was associated with Cd (positively) in placenta, but not with Zn or copper (Cu) in placenta. In conclusion, the Cd concentrations in placenta were clearly elevated, which seemed to impair Zn transfer to the fetus. Induction of MT explained the placental accumulation of Cd, but not the impairment of Zn transport.

Compliance to Intake of Prenatal Supplements among Rural Pregnant Women - an Observational Study in Two Sub-districts in Rural Bangladesh.

A cross-sectional observational study was undertaken to determine the compliance to intake of food and micronutrient supplements among 48 rural pregnant women in two sub-districts under two Divisions of Bangladesh. All pregnant women were observed from 8am to 2pm everyday for three consecutive days. Results shows that only 27.1% of the pregnant women consumed the full packet of food supplements, 43.1% shared it with other members of their family and 29.2% did not go to collect the supplement. A total of 93.8 % women did not consume the micronutrients, iron or folate supplements during the time of observation. Necessary steps should be taken to improve delivery strategies of supplements among rural pregnant women in Bangladesh, which should include training of the service providers and health education to the pregnant women.

Effects of in utero arsenic exposure on child immunity and morbidity in rural Bangladesh.

Chronic exposure to arsenic, a potent carcinogen and toxicant, via drinking water is a worldwide public health problem. Because little is known about early-life effects of arsenic on immunity, we evaluated the impact of in utero exposure on infant immune parameters and morbidity in a pilot study. Pregnant women were enrolled at 6-10 weeks of gestation in Matlab, a rural area of Bangladesh, extensively affected by arsenic contamination of tubewell water. Women (n=140) delivering at local clinics were included in the study. Anthropometry and morbidity data of the pregnant women and their children, as well as infant thymic size by sonography were collected. Maternal urine and breast milk were collected for immune marker and arsenic assessment. Maternal urinary arsenic during pregnancy showed significant negative correlation with interleukin-7 (IL-7) and lactoferrin (Ltf) in breast milk and child thymic index (TI). Urinary arsenic was also positively associated with fever and diarrhea during pregnancy and acute respiratory infections (ARI) in the infants. The effect of arsenic exposure on ARI was only evident in male children. The findings suggest that in utero arsenic exposure impaired child thymic development and enhanced morbidity, probably via immunosuppression. The effect seemed to be partially gender dependent. Arsenic exposure also affected breast milk content of trophic factors and maternal morbidity.

Phase II trial of cisplatin, interferon alpha-2b, doxorubicin, and 5-fluorouracil for biliary tract cancer.

The aim of this study was to test the efficacy of a chemotherapy combination of cisplatin, IFN alpha-2b, doxorubicin, Adriamycin, and 5-fluorouracil (PIAF) as treatment for radiologically measurable cancer of the biliary tree. Forty-one patients (19 gallbladder carcinoma and 22 cholangiocarcinoma) with unresectable, histologically confirmed adenocarcinoma were registered. Starting chemotherapy doses were as follows: cisplatin, 80 mg/m(2) i.v. over 2 h; doxorubicin, 40 mg/m(2) i.v. over 2 h; and 5-fluorouracil, 500 mg/m(2) by continuous infusion daily for 3 days. IFN alpha-2b (5 x 10(6) units/m(2)) was administered s.c. before the cisplatin and daily thereafter for a total of four doses. The overall response rate was 21.1% [95% confidence interval (CI), 10-37]. For cholangiocarcinoma and gallbladder carcinoma patients, the response rates were 9.5% (95% CI, 1-32%) and 35.3% (95% CI, 14-62%), respectively. Overall median survival time was 14 months (95% CI, 9.5-18.5), 18.1 months (95% CI, 12.1-24.1) for the cholangiocarcinoma patients, and 11.5 months (95% CI, 5.9-17.1) for the gallbladder carcinoma patients. This difference was not statistically significant. The most common grade III and IV toxicities were neutropenia (41%), thrombocytopenia (20%), nausea and vomiting (34%), and fatigue (20%). In conclusion, the PIAF combination seemed more active against gallbladder carcinoma than against cholangiocarcinoma but was associated with significant toxicity. Therefore, this regimen cannot be recommended for cholangiocarcinoma, but it may have a role in the treatment of gallbladder carcinoma, particularly among patients who were refractory to higher priority investigational agents.

Effects of antisense oligonucleotide to iNOS on hemodynamic and vascular changes induced by LPS.

Lipopolysaccharide (LPS) causes impaired vascular contractility proposed to be mediated by induction of nitric oxide synthase (iNOS). Antisense (AS) oligonucleotide inhibits the translation of target mRNA into functional proteins. We hypothesize that in vivo pretreatment with AS oligonucleotide targeted to iNOS mRNA can prevent LPS-induced hyporeactivity to norepinephrine (NE). Three groups of conscious male Wistar rats received one of the following: saline, AS, or mismatch (MM) oligonucleotide at 0.4 mg/kg iv at 12 and 24 h before LPS (5 mg/kg iv). The fourth group received saline only. Mean arterial pressure (MAP) and heart rate (HR) were continuously recorded before and 6 h after LPS or saline administration. Aorta, lung lavage, and lung tissue were collected for determination of iNOS protein expression and NOS activity. Small mesenteric arteries ( approximately 250 micron) were isolated, denuded of endothelium, and maintained at a constant intraluminal pressure of 40 mmHg for study in vitro. LPS produced significant tachycardia that was not altered by AS or MM oligonucleotide. AS, but not MM oligonucleotide, reduced the accumulation of cGMP, the increase in conversion of L-[3H]arginine to L-[3H]citrulline, and iNOS protein expression in tissue from LPS-treated rats. Small mesenteric arterial contraction to NE was significantly impaired in vessels from LPS-treated rats and was restored by AS, but not MM, oligonucleotide. In a rat model of septic shock, AS oligonucleotide to iNOS mRNA inhibits NOS activity and iNOS protein expression and prevents the vascular hyporeactivity to NE, which may contribute to hypotension in shock.

Vascular and hemodynamic effects of behavioral stress in borderline hypertensive and Wistar-Kyoto rats.

In borderline hypertensive rats (BHR), behavioral stress produces hypertension, which has been attributed to increases in sympathetic nervous system activity and peripheral changes in vascular structure. However, the mechanisms mediating development of stress-induced hypertension have not been well defined. Experiments were designed to determine hemodynamic effects and changes in small mesenteric artery (approximately 300 microns) vascular reactivity in response to 10 days of air-jet stress (2 h/day) in BHR and in Wistar-Kyoto (WKY) rats. The acute stress-induced increase in mean arterial pressure (AP) was impaired in WKY rats compared with BHR on day 1, and habituation developed to the increase in AP in BHR, but not WKY rats. Conversely, WKY rats adapted to the stress-induced tachycardia to a larger extent than BHR. The mechanisms mediating endothelium-dependent relaxation to acetylcholine (ACh) were altered in small mesenteric arteries isolated from WKY rats and BHR after 10 days of air-jet stress. Inhibition of nitric oxide synthase activity had a significantly larger inhibitory effect on ACh-induced relaxation in vessels from stressed compared with control BHR. Also, cyclooxygenase products contributed to ACh-induced relaxation of small mesenteric arteries from stressed WKY rats, but not control WKY rats. Endothelium-independent relaxation to nitroprusside was impaired in vessels from stressed WKY rats, but not stressed BHR. Finally, contraction to phenylephrine was impaired in vessels from stressed BHR, but not WKY rats. In conclusion, changes in vascular reactivity induced by air-jet stress appear to correlate with, and may contribute to, the differential hemodynamic adaptations to stress observed in WKY rats and BHR.

Anesthesia with sodium pentobarbital enhances lipopolysaccharide-induced cardiovascular dysfunction in rats.

Lipopolysaccharide (LPS)-induced hypotension and impaired aortic contraction to norepinephrine (NE) are thought to be consequent to induction of nitric oxide synthase (iNOS). Anesthesia is often employed in studies of the mechanisms mediating LPS-induced cardiovascular dysfunction in rats. Since sympathetic nervous system activity and compensatory mechanisms can be altered by anesthesia, this study was designed to determine a) if the cardiovascular dysfunction associated with LPS (5 mg/kg, i.v.)-induced endotoxin shock is enhanced in anesthetized compared with conscious male Wistar rats, and b) the potential role of iNOS in these responses to LPS. Arterial pressure and heart rate were continuously measured via a femoral arterial cannula. Six hours after LPS, conscious rats had a stable mean arterial pressure (MAP) and were tachycardic, while anesthetized rats showed a significant decrease in MAP without tachycardia. Small mesenteric arterioles (200-300 microns) were isolated, and the endothelium was removed six h after LPS. Intraluminal diameter was continuously recorded while vessels were maintained at a constant intraluminal pressure of 40 mmHg. Norepinephrine-induced contraction and oscillations/min were impaired to a greater extent in arterioles from LPS-treated anesthetized rats than in those from conscious rats. Calcium-dependent and -independent nitric oxide formation, reflected as cGMP accumulation, were also determined in aortic rings treated with a chelator of Ca2+, EGTA, or the inhibitor of nitric oxide synthase activity, L-NAME. In rings from saline-treated conscious and anesthetized rats, cGMP accumulation was significantly reduced by EGTA and L-NAME, indicating calcium-dependent constitutive (cNOS) activity. However, in aortic rings from LPS-treated conscious and anesthetized rats, cGMP accumulation was not affected by EGTA and was significantly greater in rings from anesthetized vs. conscious rats. These results suggest that cardiovascular dysfunction is more prominent in LPS-treated anesthetized vs. conscious rats. This effect may be related to increased induction of iNOS in the presence of anesthesia.