Shear Wave Elastography May Be Superior to Greyscale Median for the Identification of Carotid Plaque Vulnerability: A Comparison with Histology.

PURPOSE: There is a need to develop methods that reliably quantify characteristics associated with vulnerable carotid plaque. Greyscale median (GSM) and shear wave elastography (SWE) are two techniques that may improve individual plaque risk stratification. SWE, which quantifies Young's Modulus (YM) to estimate tissue stiffness, has been researched in the liver, breast, thyroid and prostate, but its use in carotid plaques is novel. MATERIALS AND METHODS: The aim of this study was to quantify YM and GSM of plaques and compare to histology. 25 patients (64% male) with a mean age of 76 underwent both clinical and SWE imaging. The mean GSM was quantified over a cardiac cycle. The mean YM was quantified in multiple regions within the plaque over 5 frames. Histological features were assessed following carotid endarterectomy. RESULTS: The mean YM of unstable plaques was significantly lower than that of stable plaques (50.0 kPa vs. 79.1 kPa; p = 0.027). The presence of intra-plaque hemorrhage, thrombus and increasing numbers of foam cells was also associated with a significantly lower YM. Plaque YM did not correlate well with plaque GSM (r =  .12). The mean plaque GSM was the same in both unstable and stable plaques. Fibrous plaques had a significantly higher GSM (p = 0.036). CONCLUSION: In conclusion, SWE provides additional information on plaque stiffness which may be of clinical benefit to help identify vulnerable plaque, and warrants further study.

Beyond pregnancy--the neglected burden of mortality in young women of reproductive age in Bangladesh: a prospective cohort study.

OBJECTIVE: To describe proportionate mortality and causes of death unrelated to pregnancy. DESIGN: Prospective cohort study. SETTING: Rural northwest Bangladesh. POPULATION: A cohort of 133,617 married women of reproductive age. METHODS: Verbal autopsies were conducted for women who died whilst under surveillance in the cohort trial. Physician-assigned causes of death based on verbal autopsies were used to categorise deaths. MAIN OUTCOME MEASURES: The proportion of deaths due to non-communicable diseases, infectious diseases, injury or pregnancy. RESULTS: Of the 1107 deaths occurring among women between 2001 and 2007, 48% were attributed to non-communicable diseases, 22% to pregnancy, 17% to infections, 9% to injury and 4% to other causes. CONCLUSIONS: Although focus on pregnancy-related mortality remains important, more attention is warranted on non-communicable diseases among women of reproductive age.

Supplementation with vitamin A early in life and subsequent risk of asthma.

Animal models suggest that vitamin A deficiency affects lung development adversely and promotes airway hyperresponsiveness, and may predispose to an increased risk of asthma. We examined the long-term effects of vitamin A supplementation early in life on later asthma risk. In 2006-2008, we revisited participants from two cohorts in rural Nepal who were enrolled in randomised trials of vitamin A supplementation. The first cohort received vitamin A or placebo for <16 months during their pre-school years (1989-1991). The second cohort was born to mothers who received vitamin A, ß-carotene or placebo before, during and after pregnancy (1994-1997). At follow-up, we asked about asthma symptoms and performed spirometry. Out of 6,421 subjects eligible to participate, 5,430 (85%) responded to our respiratory survey. Wheezing prevalence during the previous year was 4.8% in participants aged 9-13 yrs and 6.6% in participants aged 14-23 yrs. We found no differences between the vitamin A supplemented and placebo groups from either trial in the prevalence of lifetime or current asthma and wheeze or in spirometric indices of obstruction (p ≥ 0.12 for all comparisons). Vitamin A supplementation early in life was not associated with a decreased risk of asthma in an area with chronic vitamin A deficiency.

Acute computed tomography findings in patients with acute confusion of non-traumatic aetiology.

BACKGROUND: A retrospective review was undertaken of all patients referred for computed tomography (CT) scans of the head for acute onset of confusion, not consequent on head trauma, during the period June 1, 2004 to May 31, 2007. METHOD: Data were obtained by Microsoft Word search of the reports of the Radiology Department of the University Hospital of the West Indies, Kingston, Jamaica. Two hundred and twenty-one patients were reviewed: 103 men and 118 women. The mean age of the sample was 64 years; 168 patients (76%) were 50 years old or older. RESULT: Computed tomography scans were reported normal in 170 (76.9%) patients; 45 patients (20.4%) had definite acute intracranial CT findings. Findings were equivocal in three patients (1.4%) and unavailable for three (1.4%); 23.2% and 15.6% of patients above and below the age of 50 years respectively showed acute abnormalities on CT The most common acute finding on CT scan was an ischaemic infarct (68%). Other abnormalities included intracerebral haemorrhage and metastases 6.2% each, toxoplasmosis and primary brain tumour 4.2% each and subdural haematoma and meningitis 2.1% each. The diagnoses of toxoplasmosis were made based on appearances typical of toxoplasmosis on CT scans in patients whose request stated that they were HIV positive. CONCLUSION: In the sample reviewed, most patients who presented with acute confusion were above the age of 50 years. Overall, 20.4% of patients from all age groups had acute abnormalities on CT with a relative higher proportion, 23.2% versus 15.6% of those over 50 years, having acute pathology. The most common abnormality was an ischaemic infarct. This finding is similar to that in developed countries and unlike that seen in other developing countries where infectious aetiologies predominate.

Association between nutritional status and positive childhood disability screening using the ten questions plus tool in Sarlahi, Nepal.

The study was conducted to examine the association between the indicators of malnutrition and disability of children as reported by caregivers. The Ten Questions Plus questionnaire was administered to caregivers of 1,902 children aged 1-9 years, during August 2007-March 2008, in rural Nepal. Height and weight of children were also measured. The main outcome was a positive response to one or more questions. In total, 514 (27%) children had a positive response to at least one question. Moderate stunting [odds ratio (OR)=1.47, 95% confidence interval (CI) 1.02-2.12) and severe (OR=2.39, 95% CI 1.60-3.57) stunting were independently associated with reported delay in sitting, standing, or walking. Severe stunting was also associated with report of delayed learning compared to other children of similar age (OR=2.01, 95% CI 1.27-3.20). Parental report of disability was quite prevalent in this setting, with over a quarter of the sample screening positive. Chronic malnutrition may be associated with delayed motor and mental development.

Degenerative disc disease of the lumbar spine on MRI.

UNLABELLED: A retrospective analysis was done of all patients referred for MRI of the lumbar spine at the University Hospital of the West Indies, Kingston, Jamaica, during the three-year period January 1, 2005 and December 31, 2007. Data were collected to determine patients 'age, gender, weight and the presence or absence of degenerative disc disease (DDD). The patients' presenting symptoms were not evaluated. There were 362 patients examined: 154 males, 204 females and four uncharacterized, aged between 8 and 87 (mean age = 50.45) years. Degenerative Disc Disease (DDD), was found in 283 (78.2%) patients: 121 males, 159 females and three unidentified, with a total of 669 degenerate discs. L 4/5 and L 5/S 1 were most frequently affected accounting for 31.2% and 30.6% of degenerate discs respectively. Patients with DDD were significantly heavier and significantly older than patients without disc disease. Gender was not predictive of DDD in general nor of involvement of any particular disc though a marginally significant tendency was found for males to more frequently have DDD at L1/2 and L5/S1. CONCLUSION: Degenerative disc disease of the lumbar spine occurred more frequently in older and heavier patients. Gender did not affect the presence or the extent of the disease; compared to females, males showed a marginally increased tendency to have DDD at L1/2 and L5/S1.

Cholelithiasis on imaging--an analysis of clinical presentations by age and gender in a Jamaican population.

OBJECTIVE: This study is a descriptive analysis of the clinical presentations in which cholelithiasis was diagnosed on imaging over a five-year period at the University Hospital of the West Indies, Jamaica and how the clinical presentation varied with age and gender. METHOD: A retrospective review was done of all cases of cholelithiasis recorded in the reports of the Radiology section during the period January 1, 2002 to December 31, 2006. Patients' age and gender were noted. Each case was assigned to one of four clinical categories based on the clinical scenario at the time of referral for imaging: Acute abdomen-Incidental: (not referable to the biliary tract); Acute abdomen-Biliary (biliary colic/acute cholecystitis); Non-acute-Incidental: (not referable to the biliary tract) and Non-acute-Biliary (suspected cholelithiasis). The data were analyzed using post-hoc cross-tabulations, ANOVA, and post-hoc Tukey-tests. RESULTS: Three hundred and forty-four females and 137 males were diagnosed with cholelithiasis with the mean age at diagnosis being 49 and 50 years respectively. Females were diagnosed with cholelithiasis at higher rates in the context of acute abdominal symptoms both referable and unrelated to the biliary tract, while males were diagnosed at higher rates as an incidental finding in a non-acute presentation. There was no significant difference between the genders in the rate of diagnosis of cholelithiasis when this was suspected clinically in the non-acute setting. CONCLUSION: More females were diagnosed with cholelithiasis. There was no gender-related difference in the mean age at which cholelithiasis was diagnosed. There were statistically significant differences between the genders in the rates at which cholelithiasis was identified in different clinical scenarios.

Sex differences in the early life correlates of natural antibody concentrations.

Innate-like B1a lymphocytes arise from long-lived progenitors produced exclusively by fetal stem cells. Any insults coinciding with this early lymphopoietic wave could have a permanent impact on the B1a population and its unique protein products, the natural antibodies (NAb). We investigated early life nutritional influences on NAb concentrations of pre-adolescent children (n=290) in rural Nepal for whom we had extensive information on exposures from pregnancy and early infancy. Infant size and growth were strongly associated with NAb concentrations at 9-13 years of age among males (e.g., for neonatal weight: ßBOYS=0.43; P<0.001), but not females (e.g., for neonatal weight: ßGIRLS=-0.16; P=0.26). In females, season of birth was associated with NAb concentrations, with marked reductions among girls born during the pre-monsoon (March-May; ßGIRLS=-0.39; P=0.01) and pre-harvest (September-November; ßGIRLS=-0.35; P=0.03) seasons. Our findings suggest that nutritional or other environmental influences on immune development may vary by sex, with potential consequences for immune function during infancy and long-term risk of immune-mediated disease.

Interactions between zinc and vitamin A: an update.

Zinc status influences several aspects of vitamin A metabolism, including its absorption, transport, and utilization. Two common mechanisms postulated to explain this dependence relate to 1) the regulatory role of zinc in vitamin A transport mediated through protein synthesis, and 2) the oxidative conversion of retinol to retinal that requires the action of a zinc-dependent retinol dehydrogenase enzyme. However, evidence of an effect of zinc intake on vitamin A status from animal experiments is inconclusive, mainly because of the use of inadequate control groups. The higher weight gain of control animals as compared with the zinc-deficient ones in these experiments, even though pair fed, makes it difficult to isolate effects of zinc deficiency per se from those of generalized protein-energy malnutrition. A curvilinear relation has been suggested to describe an effect of plasma zinc on vitamin A transport. In humans, cross-sectional studies have more often than not shown a weak linkage between vitamin A and zinc status. Randomized trials have failed to show a consistent effect of zinc supplementation on vitamin A status. In disease states in which liver function is severely compromised and both zinc and vitamin A metabolism and transport are impaired, serum zinc and vitamin A concentrations tend to be positively correlated. In conclusion, clear evidence of synergy between these 2 micronutrients and its public health significance in humans is lacking. Research should focus on understanding this interaction in the context of coexisting moderate-to-severe zinc and vitamin A deficiencies in the population.

Breast-feeding, weaning patterns, and the risk of xerophthalmia in Southern Malawi.

A case-control study of breast-feeding and weaning patterns associated with xerophthalmia was conducted among children aged 24-71 mo in Southern Malawi in 1983. One hundred fifty-two children with active xerophthalmia were compared to 151 clinically normal children matched on age (+/- 12 mo), sex, and village of residence. All children were initially breast-fed; however, children with xerophthalmia began weaning onto porridge (p = 0.05) and ceased breast-feeding earlier (p less than 0.01 for 24-47 mo olds), had a shorter weaning interval (p less than 0.005), and were fully weaned from the breast for a longer duration (p less than 0.025) than the controls. The association between earlier cessation of breast-feeding and subsequent xerophthalmia was strongest during the immediate post-weaning years. These findings imply a protective role for breast-feeding against xerophthalmia in early childhood.

Vitamin A supplementation and growth: a randomized community trial.

A randomized community trial was carried out in Aceh, Indonesia, 1982-1984, to assess the impact of semiannual vitamin A (VA) supplementation (60,000 micrograms RE) on preschool child growth: 229 villages were randomized to VA program and 221 to control status. One thousand thirty-two program and 980 control children aged 1-5 y were assessed and followed for 12 mo. VA program males gained an additional approximately 110 g weight at age 2-3 y (NS), 190 g at age 4 y (p less than 0.05), and 263 g at age 5 y over control males (p less than 0.01). Arm circumference and muscle area expanded 2 mm (p less than 0.05) and approximately 36 mm2 (p less than 0.05) more per year, respectively, from ages 3 to 5 y of age and more arm fat was retained at every age (p less than 0.05 at 1 and 3 y) in VA males. There were no group differences in ponderal growth for females or in linear growth for either sex. VA supplementation may improve growth where endemic deficiency exists.

Hyporetinolemia, illness symptoms, and acute phase protein response in pregnant women with and without night blindness.

We examined the association among elevations in acute phase proteins, reported illness, and hyporetinolemia in 234 pregnant Nepali women with (cases) and without (controls) night blindness. Serum alpha1-acid glycoprotein (AGP) and C-reactive protein (CRP) were inversely associated with serum retinol concentrations. Elevations in the concentration of CRP in both cases and controls and of AGP in cases were associated with significant reductions (approximately 0.2-0.3 micromol/L) in serum retinol. The risk of a low serum retinol concentration (< 0.7 micromol/L) with elevated AGP (> or = 1 g/L) and CRP (> or = 5 mg/L) concentrations was significantly higher in cases (odds ratios = 8.6 and 4.3, respectively) than in controls (odd ratios = 1.9 and 2.4, respectively). A 7-d morbidity history indicated that cases were significantly more likely than controls to report symptoms of infections of the urinary, reproductive, and gastrointestinal tracts. Only a few of these symptoms (diarrhea, nausea, and vomiting) were significantly associated with low serum retinol concentrations. Illness in the previous week and elevated CRP or AGP concentrations were synergistically associated with lower serum retinol. For example, the reduction in serum retinol in women with diarrhea and elevated AGP was 0.54 micromol/L, compared with a reduction of 0.03 micromol/L in those with diarrhea only. AGP and CRP may provide useful information about the effect of reported illness on hyporetinolemia in pregnancy. Infection-related hyporetinolemia may predispose women to night blindness during pregnancy in Nepal.

Nutritional and household risk factors for xerophthalmia in Aceh, Indonesia: a case-control study. The Aceh Study Group.

Risk factors for xerophthalmia were assessed in 466 subjects [38% with night blindness (XN), 60% with Bitot's spots (X1B), 2% with corneal xerophthalmia (X2 or X3)] under age 6 y and their village-age-sex-matched control subjects during a community trial. Socioeconomic status and hygiene standards were lowest for households of xerophthalmic children and highest for nonstudy households in the trial population, with values for control households lying in between (P less than 0.001 by linear trend). Risk of xerophthalmia increased with less frequent consumption of dark green leaves, yellow fruits, or egg during weaning, adjusted for current intake and present age [odds ratio (OR) = approximately 3.5]. Exclusion of these same foods from the current diet (except for mango and papaya in older children) was associated with a two- to ninefold excess risk of xerophthalmia, adjusted for weaning influences. Xerophthalmic children aged less than 3 y were generally at higher risk of dietary imbalance than were older children. Xerophthalmia is associated with a chronic, infrequent consumption of key vitamin A foods from weaning through early childhood.

Influence of participation on mortality in a randomized trial of vitamin A prophylaxis.

Mortality of Sumatran children living in villages randomized to participate in a vitamin A capsule (200,000 IU) distribution program who received the capsule (n = 9776) was compared with those who did not (n = 2447) and with children living in villages randomized to serve as control subjects (n = 12,173). During the 4 mo after completion of the first distribution, mortality among preschool capsule recipients was less than 4% that of nonrecipients (p less than 0.001). Mortality among preschool nonrecipients was three times that of controls (p less than 0.05), suggesting strong selection bias. The potential biologic impact on childhood mortality attributable to vitamin A supplementation is estimated to exceed the 34% previously derived from the more conservative intent-to-treat analysis. One capsule every 6 mo may provide adequate protection for the vast majority of children. The single major limitation to maximum impact appears to be inadequate program coverage.

Impression cytology: a practical index of vitamin A status.

Impression cytology was performed on 148 Indonesian preschool children of whom half had mild xerophthalmia and half were age-matched control subjects. Subjects were divided into subgroups that reflected the degree of confidence in their true vitamin A status as determined by serum vitamin A levels, clinical examination, and response to therapy. Impression cytology was considered normal if goblet cells were present and abnormal if they were absent. Thirteen of 14 (93%) children with vitamin A-responsive Bitot's spots and night blindness with base-line serum vitamin A less than 20 micrograms/dL (0.70 mumol/L) (group 1, definite deficiency) had abnormal cytology. In contrast, 17 of 18 (94%) children with normal ocular exam and serum vitamin A greater than 25 micrograms/dL (0.87 mumol/L) (group 7, least likely deficient) had normal cytology. Importantly, 12 of 26 (46%) clinically normal children with serum vitamin A levels less than 20 micrograms/dL (0.70 mumol/L) had abnormal impression cytology.

Xerophthalmia and growth in preschool Indonesian children.

Approximately 4000 preschool children in West Java, Indonesia, were examined for xerophthalmia and weighed and measured at 3-mo intervals from March 1977 to December 1978. Children recovering from xerophthalmia over a 3-mo interval gained an average of 124 g (95% CI 42-206) more over 3 mo than normal children. Their height gain was similar to normal children's. Children who developed xerophthalmia during a 3-mo period gained 199 g (95% CI 114-313) less and grew 0.28 cm (95% CI 0.12, 0.44) less than their normal peers. Children with chronic xerophthalmia gained 120 g (95% CI 49-191) less and grew 0.21 cm (95% CI 0.05-0.37) less than normal children. These data suggest that linear and ponderal growth is adversely affected by chronic and incident xerophthalmia, but that catch-up ponderal growth is experienced by children recovering from xerophthalmia.

Hyporetinolemia and acute phase proteins in children with and without xerophthalmia.

BACKGROUND: The relations among hyporetinolemia, acute phase proteins, and vitamin A status in children are unclear. OBJECTIVE: The objective was to examine the relations between acute phase proteins and plasma retinol concentrations in children with and without clinical vitamin A deficiency (Bitot spots and night blindness). DESIGN: The study was a nonconcurrent analysis of acute phase protein concentrations and other data from a previous clinical trial. Preschool children, 3-6 y of age, with (n = 118) and without (n = 118) xerophthalmia were assigned to receive oral vitamin A (60 mg retinol equivalent) or placebo and were seen at 5 wk. All children received oral vitamin A (60 mg retinol equivalent) at 5 wk. RESULTS: At baseline, alpha(1)-acid glycoprotein (AGP) was elevated in 42.9% and 23.5% (P < 0.003) and C-reactive protein (CRP) was elevated in 17.7% and 13.7% (NS) of children with and without xerophthalmia, respectively. Hyporetinolemia (retinol < 0.7 micromol/L) occurred in 61.0% and 47.4% (P < 0.04) of children with and without xerophthalmia, respectively. A history of fever, a history of cough, and nasal discharge noted on examination were each associated with elevated acute phase proteins. Vitamin A supplementation increased plasma retinol at 5 wk but had no significant effect on concentrations of acute phase proteins. CONCLUSIONS: Elevated acute phase protein concentrations and infectious disease morbidity are closely associated during vitamin A deficiency.

Chronic low intakes of vitamin A-rich foods in households with xerophthalmic children: a case-control study in Nepal.

Dietary patterns in 81 rural Nepali households with a 1-6-y-old child with a history of xerophthalmia were compared with dietary patterns of 81 households with an age-matched nonxerophthalmic control subject. Weekly food-frequency questionnaires were collected from case and control "focus" children, a younger sibling (if present), and the household 1-2 y after recruitment and treatment of cases. Control households and children were more likely than case households and children to consume vitamin A-rich foods during the monsoon (July-September) and major rice harvesting (October-December) seasons. Cases were less likely to consume preformed vitamin A-rich foods throughout the year [odds ratio (OR) = 1.2-4.5] with the strongest differences observed from October to December (OR = 2.0-4.2). Dietary risks were generally shared by younger siblings of cases, suggesting that infrequent intake of beta-carotene and preformed vitamin-A rich foods begins early in life and clusters among siblings within households, a pattern that is consistent with their higher risk of xerophthalmia and mortality. In developing countries where vitamin A deficiency is endemic, dietary counseling for children with xerophthalmia should be extended to their younger siblings. Moreover, dietary intake of preformed vitamin A may be as, or more, important as carotenoid-containing food consumption in protecting children and other members of households from vitamin A deficiency.

Efficacy of a vitamin A-fortified wheat-flour bun on the vitamin A status of Filipino schoolchildren.

BACKGROUND: Wheat flour is a possible food vehicle for vitamin A fortification. OBJECTIVE: This study assessed the efficacy of consumption of a vitamin A-fortified wheat-flour bun (pandesal) on the vitamin A status of school-age children. DESIGN: This was a double-masked clinical trial conducted in 396 and 439 children aged 6-13 y attending 4 rural schools in the Philippines. The children were randomly assigned to a vitamin A-fortified (experimental) or nonfortified (control) group. A 60-g vitamin A-fortified pandesal (containing approximately 133 microg retinol equivalents) or a nonfortified pandesal was consumed by the children 5 d/wk for 30 wk. Vitamin A status, hemoglobin concentration, anthropometric status, morbidity, and dietary intake were assessed at baseline and 30 wk later. A modified relative dose response (MRDR) was assessed in a subsample of 20% of the children ( approximately 75/group) with the lowest initial serum retinol concentration at the 30-wk follow-up. RESULTS: Baseline serum retinol significantly modified the effect of the intervention. The fortified group, whose initial serum retinol concentrations were below the median, had a 0.07 +/- 0.03-micromol/L greater improvement in serum retinol at the 30-wk follow-up than did the control group (P: = 0.02). Improved vitamin A status was also evident in the MRDR subsample. End-of-study differences in the MRDR showed that vitamin A- fortified pandesal intake decreased the percentage of children with inadequate liver vitamin A stores by 50% (15.3% compared with 28.6%; P: = 0.05). CONCLUSIONS: Daily consumption of vitamin A-fortified pandesal significantly improved the vitamin A status of Filipino school-age children with marginal-to-low initial serum retinol concentrations.