Immigrant Mother and Her Child

The health risks of 1,164 immigrant Asian mothers and their babies in Bradford were compared with those of an indigenous group from obstetric data collected between 1965 and 1969. The average number of children for families in each group in 1969 were 3·31 and 2·33, respectively; 43·9% of 2,206 Asian mothers delivered in 1968-9 had less than a one-year interval between pregnancies. In 1965 the perinatal mortality rates for the two groups were 48·6 and 26·6, respectively, whereas in 1969 the corresponding figures were 26·8 and 25·5, respectively. Though the risks to maternal and child health of Asians are greater, Asian families are more stable and their children have a more secure upbringing than non-Asian children. However, Asian children need increased environmental stimulus in early childhood to prevent educational disadvantages at a later age.     

Factors protective against retinopathy in insulin-dependent diabetics free of retinopathy for 30 years

To investigate which factors might protect against the development of retinopathy 40 insulin-dependent diabetics who had remained free from retinopathy despite diabetes of long duration (mean±1 SD 30±10 years) were compared with 40 patients who had background and 47 who had proliferative retinopathy (mean durations of disease 16±5 and 19±5 years respectively). The three groups had had similar mean ages at onset of diabetes. The mean of all postprandial blood glucose measurements at hospital clinics from diagnosis of diabetes to detection of retinopathy, or to the most recent negative eye examination, was 9·9±2·1 mmol/l (178±38 mg/100 ml) in the group with no retinopathy, 11·8±2·1 mmol/l (213±38 mg/100 ml) in those with background retinopathy, and 12·4±2·1 mmol/l (223±38 mg/100 ml) in those with proliferative retinopathy (p <0·0001). This difference was not reflected in present concentrations of haemoglobin A_1C, probably because glycaemic control had been improved after the development of retinopathy. In the groups with background and proliferative retinopathy there were significant negative correlations between mean blood glucose concentrations and the number of years that had elapsed from diagnosis of diabetes to detection of retinopathy, suggesting that the development of both grades of retinopathy depends on the degree and duration of glycaemic exposure.The patients with no retinopathy had attended clinic more frequently (p <0·025), more of them had required emergency hospital treatment for hypoglycaemia (p <0·0025), and they tended to have had a lower prevalence of hyperglycaemic coma than the other groups. Although mean percentage ideal body weight and diastolic blood pressure were lower in the patients with no retinopathy at the time of study, mean body weight, blood pressure, and the prevalence of smoking in the years before the development of retinopathy had been similar in all groups, suggesting that these did not influence the development of retinopathy.     

Integrated Source Case Investigation for Tuberculosis (TB) and HIV in the Caregivers and Household Contacts of Hospitalised Young Children Diagnosed with TB in South Africa: An Observational Study

Background

Contact tracing, to identify source cases with untreated tuberculosis (TB), is rarely performed in high disease burden settings when the index case is a young child with TB. As TB is strongly associated with HIV infection in these settings, we used source case investigation to determine the prevalence of undiagnosed TB and HIV in the caregivers and household contacts of hospitalised young children diagnosed with TB in South Africa.

Methods

Caregivers and household contacts of 576 young children (age ≤7 years) with TB diagnosed between May 2010 and August 2012 were screened for TB and HIV. The primary outcome was the detection of laboratory-confirmed, newly-diagnosed TB disease and/or HIV-infection in close contacts.

Results

Of 576 caregivers, 301 (52·3%) self-reported HIV-positivity. Newly-diagnosed HIV infection was detected in 63 (22·9%) of the remaining 275 caregivers who self-reported an unknown or negative HIV status. Screening identified 133 (23·1%) caregivers eligible for immediate anti-retroviral therapy (ART). Newly-diagnosed TB disease was detected in 23 (4·0%) caregivers. In non-caregiver household contacts (n = 1341), the prevalence of newly-diagnosed HIV infection and TB disease was 10·0% and 3·2% respectively. On average, screening contacts of every nine children with TB resulted in the identification of one case of newly-diagnosed TB disease, three cases of newly diagnosed HIV-infection, and three HIV-infected persons eligible for ART.

Conclusion

In high burden countries, source case investigation yields high rates of previously undiagnosed HIV and TB infection in the close contacts of hospitalised young children diagnosed with TB. Furthermore, integrated screening identifies many individuals who are eligible for immediate ART. Similar studies, with costing analyses, should be undertaken in other high burden settings–integrated source case investigation for TB and HIV should be routinely undertaken if our findings are confirmed.     

Plasma TSH and Serum T-4 Levels in Long-term Follow-up of Patients Treated with 131I for Thyrotoxicosis

In February 1972 58% of patients euthyroid after iodine-131 therapy given for thyrotoxicosis between 1954 and 1966 had a high plasma TSH (>7·4 μU/ml) and 42% a normal plasma TSH level. A group of 69 of the euthyroid patients with high plasma TSH levels (25·0±2·0 μU/ml) in 1972 were re-examined 15 and 24 months later. The mean plasma TSH in the 66 patients remaining euthyroid at 15 months was 22·6±1·8 μU/ml, while three patients had become hypothyroid. At 24 months 64 of the patients were still available for study, of whom 61 remained euthyroid with a mean plasma TSH of 21·6±2·0 μU/ml, and a further three had become hypothyroid.All of a group of 61 of the euthyroid patients with normal plasma TSH levels (4·0±0·2 μU/ml) in 1972 remained euthyroid at 24 months with a mean plasma TSH of 4·1±0·3 μU/ml, though the plasma TSH level had become slightly raised in three.The mean serum T-4 level in the euthyroid patients with a high plasma TSH was significantly lower, though still in the normal range, than that in the euthyroid patients with a normal plasma TSH both in 1972 and in 1974.Since no patient with a normal plasma TSH level after iodine-131 treatment six to 18 years earlier for thyrotoxicosis developed hypothyroidism over a two-year period, the follow-up of such patients need not be so rigorous as that of similarly treated euthyroid patients with raised plasma TSH levels in whom hypothyroidism developed at the rate of 5% per year.     

Plasma Osmolality and Feeding Practices of Healthy Infants in First Three Months of Life

Plasma osmolality was measured in 60 healthy infants aged 1 to 3 months. The mean plasma osmolality in the 14 breast-fed infants (group A) was 284·3 mOsm/1. Nine infants fed artificial milk formulae alone (group B) had a mean value of 293·8 mOsm/1.; 37 infants already receiving solid foods in addition to artificial milk formulae (group C) had a mean value of 297·1 mOsm/1. The number of individual observations in the hyperosmolar range (more than 300 mOsm/1.) in groups A, B, and C were 0, 1, and 15, accounting respectively for 0%, 11·1%, and 40·5% of the total number of observations in each group.These results suggest that the early introduction to solid foods and the widespread use of artificial milk formulae at the expense of breast-feeding during the first three months of life result in an excessive dietary solute intake. This considerably stretches the ability of the immature kidney to maintain normal plasma tonicity. Minimal loss of water could precipitate a dangerous situation for babies with hyperosmolar plasma.     

Haemoglobin Belfast 15 (A12) Tryptophan→Arginine: A New Unstable Haemoglobin Variant

A new unstable haemoglobin, α₂β₂15 Trp→ Arg (Hb Belfast), with increased oxygen affinity has been found during the routine investigation of a long-stay psychiatric patient. It seemed to cause little haematological disorder. The reticulocytes synthesized normal and abnormal β-chains at the same rate but in the circulating blood Hb Belfast amounted to only 27·5% of the total haemoglobin.     

Is Screening for Cancer Worth While? Results from a Well-woman Clinic for Cancer Detection

1,768 women were screened for breast and cervical cancer in the year May 1968 to April 1969. Clinical examination followed the completion of a simple questionary. Investigations included thermography and mammography of the breast and cytology of the cervical and vaginal smears. Breast cancer was detected in 15 patients (0·85% or 8·5 per 1,000) and none was aware of any abnormality though 13 of the tumours were clinically palpable. Carcinoma in situ of the cervix was found in a further eight (0·45% or 4·5 per 1,000).     

Endocrine Changes in Premature Labour

Plasma oestradiol and progesterone levels in peripheral blood have been studied before and during premature labour of unknown aetiology. Hormones were measured by radio-immunoassay using specific antisera. Levels in patients who delivered prematurely were compared with levels measured serially in 33 primigravidae during normal pregnancy and labour.In 19 out of 25 patients admitted in progressive premature labour the plasma oestradiol level was two standard deviations or more above the mean for the control patients of similar gestational age. The mean (± S.E. of mean) plasma oestradiol in premature labour was 19·1 ± 1·1 ng/ml, similar to levels found in labour at term (18·5 ± 1·4 ng/ml). In contrast, in over 50% of cases levels of plasma progesterone during premature labour lay below the mean for gestation though within the normal range. In six patients studied serially oestradiol levels rose dramatically, high values being detected one to 10 days before the onset of premature labour. Serial progesterone levels gave no consistent trend though one patient showed steadily decreasing values.These studies suggest that the onset of premature labour is preceded by a marked increase in peripheral plasma oestradiol levels, which may be of value not only in the prediction of premature labour but also in its prevention by suppression of the premature oestradiol surge.     

Clinical Trial of Iron Therapy on Psychomotor Function in Anaemic Women

A variety of aspects of psychomotor function were assessed in 47 women before and after iron therapy. These women, all of whom had initial haemoglobin levels below 10·5 g./100 ml., had been drawn from a population sample of 2,283 women seen at a haematological screening survey. There was no evidence of any beneficial effect of a rise in haemoglobin level on psychomotor function or on symptoms. Possibly this is because if an effect does occur it is unlikely to be apparent unless the haemoglobin level is very low. If this is true then anaemia is probably a rare cause of symptoms or impairment in psychomotor function in the community.     

Clinical Problems: Hepatitis in Dialysis Units in the United Kingdom

A prospective study of hepatitis in 20 dialysis units in the United Kingdom showed that the number of units with outbreaks increased from one in 1968 to three in 1969 and the overall attack rate rose from 1·7 to 5·3% in patients and from 0·5 to 1·3% in staff.In July 1969 a pilot study of patients'' sera showed that all of the outbreaks were associated with Australia (Au) antigen. Au antigen was not detected in the unaffected units or in one unit in which there were several patients with abnormal liver function.In January 1970 systematic prospective testing for Au antigen was begun. Au antigen was detected in single patients in five more of the 20 units. The transfer of the affected patients to isolation for dialysis seemed to prevent the spread of infection in the units. The incidence of hepatitis in 1970 was 5·6% in patients and 0·4% in staff.     

Prospective Study of Serum Cholesterol Levels during First Year of Life

A longitudinal prospective study of serum cholesterol concentrations during the first year of life has been carried out in 302 healthy babies. The results show that serum cholesterol estimations in cord blood cannot be used as a screening test for the diagnosis of familial hypercholesterolaemia. The only child subsequently found to have the condition had a cord serum cholesterol of 85 mg/100 ml compared with the mean value for the group of 78 mg/100 ml. The babies who had cord values greater than 100 mg/100 ml had values distributed throughout the normal range when re-examined at 1 year of age. Serum cholesterol concentrations during the early months of life were markedly influenced by the type of milk fed; it is suggested that investigations to establish the diagnosis of familial hypercholesterolaemia are deferred until the child is about 1 year old and feeding with cows'' milk and mixed diet is established.Values obtained for serum cholesterol concentrations (mg/100 ml, mean ± 1 S.D.) in healthy infants in this study were: at birth 78 ± 23, at 1 week 155 ± 31, at 6 weeks 155 ± 31, at 4 months 184 ± 36, at 8 months 195 ± 37, and at 1 year 191 ± 36.     

Variation in haematological parameters in children less than five years of age with asymptomatic Plasmodium infection: implication for malaria field studies

During the season of high malaria transmission, most children are infected by Plasmodium, which targets red blood cells (RBCs), affecting haematological parameters. To describe these variations, we examined the haematological profiles of two groups of children living in a malaria-endemic area. A cross-sectional survey was conducted at the peak of the malaria transmission season in a rural area of Burkina Faso. After informed consent and clinical examination, blood samples were obtained from the participants for malaria diagnosis and a full blood count. Of the 414 children included in the analysis, 192 were not infected with Plasmodium, whereas 222 were asymptomatic carriers of Plasmodium infection. The mean age of the infected children was 41.8 months (range of 26.4-57.2) compared to 38.8 months (range of 22.4-55.2) for the control group (p = 0.06). The asymptomatic infected children tended to have a significantly lower mean haemoglobin level (10.8 g/dL vs. 10.4 g/dL; p < 0.001), mean lymphocyte count (4592/µL vs. 5141/µL; p = 0.004), mean platelet count (266 x 103/µL vs. 385 x 103/µL; p < 0.001) and mean RBC count (4.388 x 106/µL vs. 4.158 x 106/µL; p < 0.001) and a higher mean monocyte count (1403/µL vs. 1192/µL; p < 0.001) compared to the control group. Special attention should be applied when interpreting haematological parameters and evaluating immune responses in asymptomatic infected children living in malaria-endemic areas and enrolled in vaccine trials.     

Treatment of Hypothyroidism: A Reappraisal of Thyroxine Therapy

Twenty-two subjects with hypothyroidism have been studied in detail before and during replacement therapy with L-thyroxine (T-4). All subjects were stabilized on the minimum dose of T-4 which was necessary to suppress their serum thyroid-stimulating hormone (TSH) concentration to normal, and on this dose most subjects had a normal or impaired TSH response to thyrotrophin-releasing hormone (TRH). The daily dose of T-4 required to suppress TSH was 0·1 mg (13 subjects), 0·15 mg (six subjects), and 0·2 mg (three subjects). It was shown that all subjects were euthyroid on these doses and, using a range of thyroid function tests, that they were normal in all respects when compared with a group of euthyroid controls, with the exception of a small group who had a marginally raised serum triiodo-L-thyronine (T-3) concentration. It has been shown that those subjects who required the larger doses of T-4 had a more advanced degree of thyroid failure than those who were stabilized on 0·1 mg T-4 daily. It is concluded that conventional doses of T-4 (0·2-0·4 mg daily) are often associated with subclinical hyperthyroidism.     

Dynamics of G6PD activity in patients receiving weekly primaquine for therapy of Plasmodium vivax malaria

BackgroundAcute Plasmodium vivax malaria is associated with haemolysis, bone marrow suppression, reticulocytopenia, and post-treatment reticulocytosis leading to haemoglobin recovery. Little is known how malaria affects glucose-6-phosphate dehydrogenase (G6PD) activity and whether changes in activity when patients present may lead qualitative tests, like the fluorescent spot test (FST), to misdiagnose G6PD deficient (G6PDd) patients as G6PD normal (G6PDn). Giving primaquine or tafenoquine to such patients could result in severe haemolysis.MethodsWe investigated the G6PD genotype, G6PD enzyme activity over time and the baseline FST phenotype in Cambodians with acute P. vivax malaria treated with 3-day dihydroartemisinin piperaquine and weekly primaquine, 0·75 mg/kg x8 doses.ResultsOf 75 recruited patients (males 63), aged 5–63 years (median 24), 15 were G6PDd males (14 Viangchan, 1 Canton), 3 were G6PD Viangchan heterozygous females, and 57 were G6PDn; 6 patients had α/β-thalassaemia and 26 had HbE.Median (range) Day0 G6PD activities were 0·85 U/g Hb (0·10–1·36) and 11·4 U/g Hb (6·67–16·78) in G6PDd and G6PDn patients, respectively, rising significantly to 1·45 (0·36–5·54, p<0.01) and 12·0 (8·1–17·4, p = 0.04) U/g Hb on Day7, then falling to ~Day0 values by Day56. Day0 G6PD activity did not correlate (p = 0.28) with the Day0 reticulocyte counts but both correlated over time. The FST diagnosed correctly 17/18 G6PDd patients, misclassifying one heterozygous female as G6PDn.ConclusionsIn Cambodia, acute P. vivax malaria did not elevate G6PD activities in our small sample of G6PDd patients to levels that would result in a false normal qualitative test. Low G6PDd enzyme activity at disease presentation increases upon parasite clearance, parallel to reticulocytosis. More work is needed in G6PDd heterozygous females to ascertain the effect of P. vivax on their G6PD activities.Trial registrationThe trial was registered (ACTRN12613000003774) with the Australia New Zealand Clinical trials (https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=363399&isReview=true).     

Glycaemic threshold for changes in electroencephalograms during hypoglycaemia in patients with insulin dependent diabetes

The relation between blood glucose concentration, the symptoms and signs of hypoglycaemia, and electroencephalographic changes in diabetic patients is not known. The effect of hypoglycaemia on brain function was studied in 13 patients with insulin dependent diabetes. During a gradual fall in blood glucose concentration induced by a bolus injection of insulin followed by an intravenous infusion of insulin, during 60 minutes of biochemical hypoglycaemia, and after restoration of normoglycaemia with intravenous glucose electroencephalograms were evaluated continuously by period-amplitude analysis; blood samples were taken every 10 minutes throughout. No changes were seen in electroencephalograms when the blood glucose concentration was above 3 mmol/l. At a median blood glucose concentration of 2·0 (95% confidence interval 1·7 to 2·3) mmol/l alpha activity decreased abruptly in the electroencephalograms concomitant with an increase in theta activity, reflecting neuronal dysfunction in the cortex. When the blood glucose concentration was further lowered changes were observed in the electroencephalograms indicating that deeper brain structures were affected. A normal electroencephalogram was re-established at a blood glucose concentration of 2·0 (1·8 to 2·1) mmol/l. There was no significant correlation between the blood glucose concentration at the onset of changes in the electroencephalograms and age, duration of diabetes, insulin dose, haemoglobin A_1c concentration, initial blood glucose concentration, rate of fall in blood glucose concentration, and appearance of symptoms and signs of hypoglycaemia.Changes in electroencephalograms during hypoglycaemia appear and disappear at such a narrow range of blood glucose concentrations that the term threshold blood glucose concentration for the onset of such changes seems justified.     

Impaired renal functional reserve and albuminuria in essential hypertension

The stimulatory effects of an infusion of amino acids on glomerular filtration rate has previously been used to measure renal functional reserve and detect glomerular hyperfiltration. Thirty four patients with mild to moderate essential hypertension and seemingly normal renal function and 22 healthy controls were given infusions of amino acids to investigate whether renal functional reserve is reduced in essential hypertension and to detect patients at risk of renal damage. Although basal creatinine clearance increased after the infusion of amino acids in the controls (mean 27·9 ml/min; 95% confidence interval 18·2 to 37·6), the overall change was lower in the patients (mean 13·4 ml/min; 8·3 to 18·5), 11 of the 34 showing no increase at all. In these 11 non-responders the mean systolic blood pressure was higher than that in the 23 others (178·5 mm Hg v 157 mm Hg, respectively). Mean urinary albumin excretion was abnormal in the patients (93·3 mg/24 h; 44·2 to 142·4); eight of the 11 non-responders had an albumin excretion above the normal range (>20 mg/24 h). In the 11 patients without renal functional reserve a positive correlation was found between basal creatinine clearance and albumin excretion (r=0·695).As consumed renal reserve and albuminuria are markers of glomerular hyperfiltration studying renal function before and after infusion of amino acids can detect hypertensive patients at risk of progressive renal damage.     

Risk Factors for Death among Children Less than 5 Years Old Hospitalized with Diarrhea in Rural Western Kenya, 2005–2007: A Cohort Study

Background

Diarrhea is a leading cause of childhood morbidity and mortality in sub-Saharan Africa. Data on risk factors for mortality are limited. We conducted hospital-based surveillance to characterize the etiology of diarrhea and identify risk factors for death among children hospitalized with diarrhea in rural western Kenya.

Methods and Findings

We enrolled all children <5 years old, hospitalized with diarrhea (≥3 loose stools in 24 hours) at two district hospitals in Nyanza Province, western Kenya. Clinical and demographic information was collected. Stool specimens were tested for bacterial and viral pathogens. Bivariate and multivariable logistic regression analyses were carried out to identify risk factors for death. From May 23, 2005 to May 22, 2007, 1,146 children <5 years old were enrolled; 107 (9%) children died during hospitalization. Nontyphoidal Salmonella were identified in 10% (118), Campylobacter in 5% (57), and Shigella in 4% (42) of 1,137 stool samples; rotavirus was detected in 19% (196) of 1,021 stool samples. Among stools from children who died, nontyphoidal Salmonella were detected in 22%, Shigella in 11%, rotavirus in 9%, Campylobacter in 5%, and S. Typhi in <1%. In multivariable analysis, infants who died were more likely to have nontyphoidal Salmonella (adjusted odds ratio [aOR] = 6·8; 95% CI 3·1–14·9), and children <5 years to have Shigella (aOR = 5·5; 95% CI 2·2–14·0) identified than children who survived. Children who died were less likely to be infected with rotavirus (OR = 0·4; 95% CI 0·2–0·8). Further risk factors for death included being malnourished (aOR = 4·2; 95% CI 2·1–8·7); having oral thrush on physical exam (aOR = 2·3; 95% CI 1·4–3·8); having previously sought care at a hospital for the illness (aOR = 2·2; 95% CI 1·2–3·8); and being dehydrated as diagnosed at discharge/death (aOR = 2·5; 95% CI 1·5–4·1). A clinical diagnosis of malaria, and malaria parasites seen on blood smear, were not associated with increased risk of death. This study only captured in-hospital childhood deaths, and likely missed a substantial number of additional deaths that occurred at home.

Conclusion

Nontyphoidal Salmonella and Shigella are associated with mortality among rural Kenyan children with diarrhea who access a hospital. Improved prevention and treatment of diarrheal disease is necessary. Enhanced surveillance and simplified laboratory diagnostics in Africa may assist clinicians in appropriately treating potentially fatal diarrheal illness. Please see later in the article for the Editors'' Summary     

Further Observations on the Relation between Iron and Folate Status in Pregnancy

This study was planned to determine whether iron deficiency in pregnancy predisposed to the development of folate deficiency and also the smallest daily iron supplement that maintained haemoglobin levels in pregnancy.Three groups of women were given oral ferrous fumarate supplying 30, 60, and 120 mg of iron; a fourth group was given 1 g of parenteral iron in early pregnancy followed by oral iron (60 mg); a fifth group received a placebo. Tablets were taken once daily.Oral iron 30 mg once daily maintained haemoglobin levels throughout pregnancy. Women whose marrows lacked demonstrable iron at the 37th week had a significantly higher incidence of megaloblastic haemopoiesis (28·7%) than those with demonstrable iron stores (15·3%); women taking oral iron did not have a lower frequency of megaloblastosis than those given a placebo. We concluded that iron does not have a direct effect on folate status in pregnancy, that the association of iron deficiency and megaloblastic anaemia in pregnancy is the result of poor nutrition, and that there is no cause-and-effect relation between them.     

Measles Virus-Specific IgG in Cerebrospinal Fluid in Multiple Sclerosis

The prevalence of measles virus-specific IgG in cerebrospinal fluid (C.S.F.) of patients with multiple sclerosis (M.S.) has been compared with that in fluids from patients with other neurological diseases and from normal control subjects. The prevalence in the three groups was 58·1%, 24·1%, and 0% respectively. Fivefold concentration of the specimens increased the prevalence in the first two groups to 80·6% and 34·5% respectively, while measles IgG was not detected in any fluids of the normal control group, even after concentration.     

Thermal,Metabolic, Blood,and Circulatory Adjustments in Prolonged Outdoor Exercise

Thermal, metabolic, and circulatory responses were studied in six hill-walkers taking part in a 28-mile (45-km.) walk in rough country in autumn and winter, air temperatures being 6 to 12° C. and –2 to 2° C., respectively.Though they were an apparently well-matched party, the walkers had to split into three pairs to avoid exhaustion. They adjusted their clothing so that mean skin temperatures were similar in both warm and cold conditions, the average value being 30·5° C. compared with the resting comfort range of 33 to 34·5° C. When, on the winter trial, skin temperatures were lowered by reduction of clothing, mean skin temperatures fell to 26·5 to 27·8° C., one subject showing a value of 21·3° C. These temperatures were associated with moderate discomfort from cold.Gut temperatures during exercise, measured with a radio pill, averaged 38·7 to 37·9° C. on the autumn exercise. Slightly lower values were observed in winter, but this was associated with slower walking rather than cold stress. A fat and a thin subject walking together with minimal clothing showed widely different temperature responses, the fatter subject having a lower skin temperature and higher gut temperature than his companion. These results were compared with other results on extreme cold stress and discussed in relation to hypothermia. Heart rate and blood pressure findings were unremarkable, except for increased post-exercise heart rates and standing/lying heart rate differences, and a tendency to postural hypotension associated with exhaustion. Blood volume was not reduced in exhaustion and there were no significant changes in blood electrolytes or other constituents apart from a small rise in potassium. Ketonuria developed in all subjects.