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.

Maternal supplementation with vitamin A or ß-carotene and cardiovascular risk factors among pre-adolescent children in rural Nepal.

Vitamin A plays an important role in fetal renal and cardiovascular development, yet there has been little research on its effects on cardiovascular risk factors later in childhood. To examine this question, we followed the children of women who had been participants in a cluster-randomized, double blind, placebo-controlled trial of weekly supplementation with 7000 µg retinol equivalents of preformed vitamin A or 42 mg of ß-carotene from 1994 to 1997 in rural Nepal. Women received their assigned supplements before, during and after pregnancy. Over a study period of 3 years, 17,531 infants were born to women enrolled in the trial. In 2006-2008, we revisited and assessed 13,118 children aged 9-13 years to examine the impact of maternal supplementation on early biomarkers of chronic disease. Blood pressure was measured in the entire sample of children. In a subsample of 1390 children, venous blood was collected for plasma glucose, Hb1Ac and lipids and a morning urine specimen was collected to measure the ratio of microalbumin/creatinine. Detailed anthropometry was also conducted in the subsample. The mean ± s.d. systolic and diastolic blood pressure was 97.2 ± 8.2 and 64.6 ± 8.5 mm Hg, respectively, and about 5.0% had high-blood pressure (⩾120/80 mm Hg). The prevalence of microalbuminuria (⩾30 mg/g creatinine) was also low at 4.8%. There were no differences in blood pressure or the risk of microalbuminuria between supplement groups. There were also no group differences in fasting glucose, glycated hemoglobin, triglycerides or cholesterol. Maternal supplementation with vitamin A or ß-carotene had no overall impact on cardiovascular risk factors in this population at pre-adolescent age in rural Nepal.

Size at birth is associated with blood pressure but not insulin resistance in 6-8 year old children in rural Nepal.

Earlier, we reported that antenatal micronutrient supplementation reduced the risk of metabolic syndrome and microalbuminuria among offspring at 6-8 years of age in rural Nepal. In the same birth cohort, we examined associations of size at birth (weight, length and ponderal index), and gestational age, with cardiometabolic risk factors in childhood across all antenatal micronutrient interventions. There was an inverse association between birth weight and systolic blood pressure (SBP, ß = -1.20 mm Hg/kg; 95% confidence interval (CI): -1.93, -0.46) and diastolic blood pressure (DBP, ß = -1.24 mm Hg/kg; 95% CI: -2.00, -0.49). Current child body mass index was positively associated with SBP but not with DBP. Birth weight was unassociated with insulin resistance, but each kilogram of increase was associated with a reduced risk of high triglycerides (odds ratio (OR) = 0.64/kg; 95% CI: 0.41, 0.97) and an increased risk of high waist circumference (OR = 3.16/kg; 95% CI: 2.47, 4.41). In this rural Nepalese population of children 6-8 years of age with a high prevalence of undernutrition, size at birth was inversely associated with blood pressure and triglycerides and positively associated with waist circumference.

Weight for age charts for children with achondroplasia.

To develop accurate weight for age charts for individuals with achondroplasia. These novel weight for age, gender-specific growth curves for achondroplasia patients from birth through 16 years were constructed from a longitudinal, retrospective, single observer cohort study of 334 individuals with achondroplasia. Weight for age data from 301 subjects in this achondroplasia cohort, constituting 1,964 total weight measurements, are presented in these weight for age curves. Percentiles (5, 25, 50, 75, 95th) were estimated across the age continuum by gender, using a 1 month window (+/-0.5 months) around each time point of interest. Percentiles were smoothed using a quadratic, penalized smoother by a semi-parametric model approach. Raw weight data from the achondroplasia cohort are compared to that of average stature children presented in the current CDC growth curves, divided into 0-36 months and 2-16 years. There was overlap of birth weight between achondroplasia and average stature infants. This statistical modeling method can be applied to other anthropometric parameters collected from this achondroplasia cohort (e.g., length, BMI), other skeletal dysplasia diagnoses, and to syndromic, non-skeletal dysplasia diagnoses which may benefit from standardization of weight for age.

Calcium acquisition rates do not support age-appropriate gains in total body bone mineral content in prepuberty and late puberty in girls with cystic fibrosis.

Few longitudinal data are available characterizing bone development in adolescents with cystic fibrosis (CF) although this is a critical time for bone mineralization. Dual energy X-ray absorptiometry (DXA) scans were obtained at 1- to 4-year intervals in 18 prepubertal and pubertal girls (age 7-18 years) with CF to determine calcium (Ca) accretion rates and changes (Delta) in total body bone mineral content (TBBMC) and lumbar spine bone mineral density (LS BMD) Z-scores. Daily Ca acquisition rates were calculated assuming TBBMC was composed of 32.2% Ca. Bone Ca accretion averaged 82 mg/day (2.05 mmol/day) [(range:-38 to +197 mg/day (-0.95 to 4.9 mmol/day)] on approximately 1,200 mg/day (30 mmol/day) Ca intakes. Estimated mean peak Ca accretion was 160 mg/day (4 mmol/day) at age 13 years; losses of bone Ca occurred in late puberty. Gains in insulin-like growth factor 1 (IGF-1) predicted Ca accretion (p<0.06). Body mass index (BMI) Z-score predicted LS BMD and TBBMC Z-score cross-sectionally but did not predict DeltaTBBMC Z-score. Changes in TBBMC Z-score paralleled Ca accretion rates with age. Bone Ca accretion in girls with CF fell below rates in healthy girls during prepuberty and late puberty despite Ca intakes approaching recommendations. IGF-1 and BMI Z-scores may identify children with CF at risk of compromised bone accretion, and more data are required to elucidate roles of lung function and glucocorticoid use in compromised bone health.

Seasonality in urinary and household salt iodine content among pregnant and lactating women of the plains of Nepal.

OBJECTIVE: To determine the extent and causes of iodine deficiency among women during pregnancy and lactation in the southeastern plains of Nepal. DESIGN, SETTING AND SUBJECTS: Urinary iodine (UI) was assessed as an indicator of iodine status in spot urine samples of women participating in a field trial in three rural communities in the plains of southeastern Nepal. Samples were collected during pregnancy (n=1021) and during lactation at 3-4 months postpartum (n=1028) at a central clinic; 613 women were assessed at both times. Salt iodine (SI) content was assessed semiquantitatively at 6-7 months postpartum in households (n=1572). RESULTS: During pregnancy and lactation, median UI concentrations were 0.756 and 0.483 micromol/l, respectively, indicating mild iodine deficiency. UI and SI concentrations covaried markedly by season and were highest during hot, dry, premonsoon months and lowest during and following the humid monsoon season. Within women who contributed urine samples during both pregnancy and the postpartum period, iodine status determined by UI was not correlated. The percentage of households with adequately iodized salt (30 ppm) ranged from 85 to 44% from the hot, dry to the humid seasons, respectively. CONCLUSIONS: In the rural southern plains of Nepal, iodine deficiency remains a mild-to-moderate public health problem among pregnant and lactating women despite the availability of iodized salt. Marked seasonality in SI content may account for the lack of intraindividual correlation between maternal iodine status during pregnancy and postpartum periods and contribute to periodicity in the risk of iodine deficiency.

[Significance of subsequent hip unloading after surgical intertrochanteric osteotomy of idiopathic femur head necrosis]. / Die Bedeutung der konsequenten Entlastung nach operativ mit intertrochantären Osteotomien behandelten idiopathischen Hüftkopfnekrosen.

PURPOSE: To judge the influence of consequent non-weight-bearing on the postoperative results, we reviewed 28 patients in whom we performed intertrochanteric osteotomies for idiopathic osteonecrosis of the femoral head during the years 1996 and 1997. Postoperatively 12 patients were supplied with a walking device for non-weight-bearing which was used for 1 year. 16 patients were mobilized by using 2 crutches for 15 kp partial weight-bearing until the osteotomy healed up and were then allowed to bear full weight. METHOD: For clinical evaluation of the early results after about 18 month the Merle d'Aubigné hip score was used. Furthermore we analyzed pelvic radiographs for assessing the stage of the necrosis (Ficat staging) and the necrotic angle. RESULTS: Overall 82% good and excellent results were achieved. Due to a longer period of non-weight-bearing the results were again clearly improved (92% versus 75% of patients with partial weight-bearing). It was noticed that there were discrepancies between good clinical results and the less satisfying radiographic findings. CONCLUSIONS: Postoperative non-weight-bearing for about 1 year with the use of a walking device by patients with idiopathic osteonecrosis of the femoral head has clearly a positive effect on clinical results.

Effects of the Zanzibar school-based deworming program on iron status of children.

We evaluated the effects of the Zanzibar school-based deworming program on the iron status of primary school children. Parasitologic and nutritional assessments were carried out at baseline, 6 mo, and 12 mo in 4 nonprogram schools (n = 1002), 4 schools in which students received twice-yearly deworming (n = 952), and 4 schools in which students received thrice-yearly deworming (n = 970) with 500 mg generic mebendazole. Schools were randomly selected for evaluation and allocated to program groups. Relative to no treatment, thrice-yearly deworming caused significant decreases in protoporphyrin concentrations and both deworming regimens caused marginally significant increases in serum ferritin concentrations. The average annual changes in protoporphyrin concentrations were -5.9 and -23.5 micromol/mol heme in the control and thrice-yearly deworming groups, respectively (P < 0.001). The average changes in ferritin concentration were 2.8 and 4.5 microg/L, respectively (P = 0.07). Deworming had no effect on annual hemoglobin change or prevalence of anemia. However, the relative risk of severe anemia (hemoglobin < 70 g/L) was 0.77 (95% confidence limits: 0.39, 1.51) in the twice-yearly deworming group and 0.45 (0.19, 1.08) in the thrice-yearly deworming group. The effects on prevalence of high protoporphyrin values and incidence of moderate-to-severe anemia (hemoglobin < 90 g/L) were significantly greater in children with > 2000 hookworm eggs/g feces at baseline. We estimate that this deworming program prevented 1260 cases of moderate-to-severe anemia and 276 cases of severe anemia in a population of 30,000 schoolchildren in 1 y. Where hookworm is heavily endemic, deworming programs can improve iron status and prevent moderate and severe anemia, but deworming may be needed at least twice yearly.

[Overview of the current status of measurable parameters of cartilage metabolism in various body fluids]. / Uberblick über den aktuellen Stand der messbaren Parameter des Knorpelstoffwechsels in verschiedenen Körperflüssigkeiten.

The human cartilage and bone is characterized by a remodeling during the life, well balanced by neosynthesis and degradation of matrix components. In different joint diseases, it becomes imbalanced and the destruction of the cartilage supersedes the repair. In tissue processes in disease and in normal turnover of the matrix, these molecules are fragmented and released into surrounding fluids, in the synovial fluid, and then in the blood and the urine, where they can be detected. The quantitative measurement in the synovial fluid is more specific than in the other body fluids. The research process in recent years has suggested that these molecular markers of cartilage and bone matrix metabolism can be used to determine diagnosis, the disease severity rather than its presence or absence, the prognosis, and the response to therapy. They should help to identify the disease mechanism in different joint diseases not only on the tissue but also on the molecular level. The specific cartilage matrix markers promise to become useful tools in the future in clinical use. The research in this area is still in the early stages, with most results dated from the end of the 1980s and the 1990s.

Serum ferritin, erythrocyte protoporphyrin and hemoglobin are valid indicators of iron status of school children in a malaria-holoendemic population.

In many African populations, the prevalences of both iron deficiency and malarial infection exceed 50%. The control of iron deficiency anemia is of urgent public health importance, but assessment of iron status in these contexts has been controversial because of the effects of malarial disease on common iron status indicators. We assessed iron status in 3605 school children in Zanzibar by measuring hemoglobin, erythrocyte protoporphyrin (EP) and serum ferritin concentrations. Malaria parasitemia was quantified by counting against leukocytes. Iron deficiency was highly prevalent: 62.4% of hemoglobin concentrations were <110 g/L, 59.7% of EP values were >80 micromol/mol heme, and 41.5% of ferritin concentrations were <12 microg/L. Prevalence of Plasmodium falciparum parasitemia was 60.6%, but <1% of children had densities above 5000 parasites/microL blood. Neither hemoglobin nor EP concentration was associated with malaria parasite density, but prevalence of abnormal values increased by < or = 25% with parasite density. Erythrocyte protoporphyrin and hemoglobin were strongly inversely related regardless of parasite density. The relationship of EP to hemoglobin was slightly attenuated when parasite density exceeded 1000 parasites/microL blood. Ferritin rose by 1.5 microg/L per 1000 parasites/microL for parasite densities >1000 parasites/microL, but the relationship of ferritin to hemoglobin or EP was strong even when parasite densities exceeded this cutoff. The population prevalences of iron deficiency were not significantly biased by malarial infection. In this population of school children, iron status assessment using these indicators was not seriously influenced by malarial infection. We hypothesize that these indicators perform reliably in populations in which malarial infection is infrequently associated with disease; namely older children and adults in holoendemic environments.

Epidemiology of iron deficiency anemia in Zanzibari schoolchildren: the importance of hookworms.

Anemia is estimated to affect one-half of school-age children in developing countries. The school years are an opportune time to intervene, and interventions must be based on sound epidemiologic understanding of the problem in this age group. We report on the distribution of iron deficiency and anemia across age, sex, anthropometric indexes, and parasitic infections in a representative sample of 3595 schoolchildren from Pemba Island, Zanzibar. Iron status was assessed by hemoglobin, erythrocyte protoporphyrin (EP), and serum ferritin concentrations from a venous blood sample. Overall, 62.3% of children were anemic (hemoglobin < 110 g/L), and 82.7% of anemia was associated with iron deficiency. The overall prevalence of iron-deficient erythropoiesis (EP > 90 mumol/mol heme) was 48.5%, and the prevalence of exhausted iron stores (serum ferritin < 12 micrograms/L) was 41.3%. In bivariate analyses, iron status was slightly better in girls than in boys, and was better in children aged 7-11 y than in those older or younger. Hemoglobin but not EP or serum ferritin concentrations were lower in stunted children. Infection with malaria, Trichuris trichiura, Ascaris lumbricoides, and hookworms were all associated with worse iron status; the association with hookworms was strongest by far. In multivariate analyses, hookworm infection intensity was the strongest explanatory variable for hemoglobin, EP, and serum ferritin. Sex, malarial parasitemia, A. lumbricoides infection, and stunting were also retained in the multivariate model for hemoglobin. Twenty-five percent of all anemia, 35% of iron deficiency anemia, and 73% of severe anemia were attributable to hookworm infection; < 10% of anemia was attributable to A. lumbricoides, malaria infection, or stunting. We conclude that anthelminthic therapy is an essential component of anemia control in schoolchildren in whom hookworms are endemic, and should be complemented with school-based iron supplementation.

Sustained diurnal blood pressure reduction in SHR with ramipril assessed by telemetric monitoring.

Subchronic bolus administration of the angiotensin-converting-enzyme inhibitor ramipril caused a dose-dependent (0.1 to 10 mg.kg-1.d-1), yet each in his own way 24-hour sustained, reduction in arterial blood pressure in conscious unrestrained spontaneously hypertensive rats with telemetric recording, and 0.01 mg.kg-1.d-1 was a no-effect dose. This was accompanied by dose-dependent attenuation of heart rate lowering during periods of low locomotor activity. Neither effect persisted for more than a few days after cessation of the medication with full restoration of pretreatment levels. No dosage altered the circadian rhythm of blood pressure, heart rate and locomotor activity of the rats.

The BWM spinal fixator system. A preliminary report of a 2-year prospective, international multicenter study in a range of indications requiring surgical intervention for bone grafting and pedicle screw fixation.

STUDY DESIGN: A prospective, international, multicenter study of 400 patients who received the BWM fixator system. OBJECTIVES: To assess the effectiveness and safety of the system in the management of various conditions requiring spinal fixation and bone grafting. SUMMARY OF BACKGROUND DATA: The BWM system was developed for the management of spinal instability of all etiologies occurring in the thoracic, thoracolumbar, and lumbosacral spine. METHODS: Patients with fracture, tumor, spondylolisthesis, spondylitis, failed back, or other degenerative conditions of the spine received the BWM instrumentation as described in the study literature and were regularly reviewed for 2 years. RESULTS: The results from the first 200 patients to complete the study showed an overall graft fusion rate of 94% (95% confidence interval: 91.3%-97.6%). There were marked improvements in measures of functional ability (P < 0.001, Wilcoxon test). Before surgery, less than half the patients were capable of outdoor activity. At 2 years, 80% were able to undertake outdoor activity. There were few perioperative difficulties reported. Postoperative complications associated with major surgery were seen in 18% patients. There were 23 (2.6%) pedicle screw failures, including two loosenings, and 13 (2.5%) spacer element failures, including three loosenings. CONCLUSIONS: Clinical failure was not necessarily a consequence of component failure. The BWM fixator provided excellent stabilization during the process of bone graft consolidation. The risks of complication or component failure were no higher than those associated with similar devices.

Pre- and postweaning food restrictions interact to determine reproductive success and milk volume in rats.

This study was designed to determine if nutrient availability during gestation and early life modifies the effects of subsequent dietary intake on reproductive and lactation performance. Rat pups, whose mothers had been allowed free access to food or were food-restricted to 50% of ad libitum consumption were assigned to free access or food restricted groups after weaning, creating 4 groups (pre- and postweaning diet). Pre- and postweaning diets interacted significantly to influence age at conception, number of pups born, and milk yield on d 14 of lactation. Early undernutrition deterred conception in dams later allowed free access to food and resulted in fewer pups born to dams later allowed free access to food, but not those in the food-restricted group. By d 15 of lactation, only dietary treatment after weaning influenced litter weight. Milk yield per gram dam weight was not impaired in the food restricted-ad libitum group but was lowered in dams in the ad libitum-food restricted group. Milk yield per gram litter weight was not impaired in ad libitum-food restricted dams but was reduced in food restricted-ad libitum dams. These results extend to the preweaning period our previous finding that past or current food restriction impairs reproductive success and decreases milk yield in rats.

Nutritional status, suckling behavior, and prolactin release during lactation.

This experiment was conducted to determine whether suckling-induced prolactin (PRL) values in chronically food-restricted lactating rats resulted from the inability of their litters to suckle vigorously. Rats were randomly assigned to be fed ad lib (AL) or to be chronically restricted (CR) to 50% of AL before and during pregnancy and lactation. Rats nursed their own litter (own) or a litter of the opposite dietary treatment group (other) for 90-min periods at early or peak lactation. Blood was collected regularly through a catheter implanted several days earlier. Suckling contributed to differences in PRL between AL and CR dams in early lactation as demonstrated by an interaction between dietary treatment and type of litter. However, tests of AL own vs. AL other and CR own vs. CR other were not significant. This is probably because the inattentive behavior of CR dams attenuated the PRL response in this group. At peak lactation, PRL values were related to recovery time from catheter implantation; therefore, determinants of PRL release change over the course of lactation.

[Follow-up of patients with knee endoprostheses of the orthopedic clinic of the Dresden "Carl Gustav Carus" Medical Academy]. / Nachuntersuchungen von Patienten mit Knieendoprothesen der Orthopädischen Klinik der Medizinischen Akademie "Carl Gustav Carus" Dresden.

A report is given about an examination of 143 knee prostheses which were implanted between 1973 bis 1983. After biomechanic points of view the used prostheses were divided in four types. Very good to good results were found there in 70-80% of cases. Most positive results were reached by the so called sledge prostheses. In 44% of cases there were observed complications. The rate of complications is about 12% higher by patients whose basic disease is pcP.