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Biomedical subjects

J M Pettifor

Publications and source records attributed to J M Pettifor.

At least 19 recordsLinked to original sources

Differences in bone size and bone mass between black and white 10-year-old South African children.

INTRODUCTION: Black and white South Africans hail from vastly disparate cultural and socio-economic backgrounds the result of which exposes black children to numerous factors known to impact negatively on bone mass. Thus, we studied ethnic differences in bone size and bone mass between 476 10-year-old black and white South African girls and boys (black boys n=182, white boys n=72, black girls n=158, white girls n=64) who formed part of a longitudinal cohort of children born in Johannesburg, South Africa, during 1990. METHODS: Bone area (BA) and bone mineral content (BMC) were measured at the whole body, total hip, femoral neck, lumbar spine (L1-L4) and mid- and distal radii by dual energy X-ray absorptiometry (DXA). Vertebral heights and metacarpal indices were measured. Anthropometry, skeletal maturity and pubertal development were also assessed. RESULTS: After correction for height, weight, gender and puberty, black children had greater BMC at the femoral neck (P<0.0001), total hip (P<0.05) and mid-radius (P<0.001) than white children.. At the whole body, lumbar spine, and distal one-third of the radius, there were no differences in BMC between black and white children after correction for differences in body size. After correction for height and puberty, vertebral heights were less in black children than white children, and cortical areas at the second metacarpal were greater in black children. CONCLUSION: These findings suggest that, at the femoral neck, total hip and mid-radius, these differences are not a result of differences in anthropometry, bone age or pubertal stage, or environmental factors but are most likely to result from genetic differences.

Absorptiometry, Photon↗

Causes of lead toxicity in a Nigerian city.

BACKGROUND: Up to 70% of young Nigerian children have been reported to have blood lead concentrations > or =10 microg/dl. AIMS: To better elucidate risk factors for lead toxicity among Nigerian families with children at risk for lead toxicity. METHODS: Two geographic wards in Jos, Nigeria were selected for study, one previously reported to have a high mean blood lead level (37 (SD 13) microg/dl) and one with a lower mean blood lead level (17 (SD 10) microg/dl) in young children. Data pertaining to potential risk factors for lead exposure were collected from children and adults in 34 households. RESULTS: The mean (SD) blood lead concentration of 275 subjects, aged 3 weeks to 90 years, was 8.7 (5.7) microg/dl (range 1-34 microg/dl); 92 (34%) had concentrations > or =10 microg/dl. In multivariate analysis, an age of 5 years and under, flaking house paint, residence near a gasoline seller, male gender, increasing maternal and paternal education, and use of a lead ore eye cosmetic were independently associated with greater blood lead concentration. Vehicle ownership was associated with reduced lead concentration. Compared with the low-lead ward, residence in the high-lead ward remained significantly associated with greater lead values, indicating that additional factors likely contribute to lead exposure. CONCLUSION: Although the cause of increased lead levels in Jos appears to be multi-factorial, several remediable sources contribute to lead exposure in Nigeria.

Adolescent↗

Associations between physical activity and bone mass in black and white South African children at age 9 yr.

We investigated differences in physical activity (PA) levels between black and white South African 9-yr-old children and their association with bone mineral content (BMC) and density (BMD) by using dual-energy X-ray absorptiometry. PA was analyzed in terms of a metabolic (METPA; weighted metabolic score of intensity, frequency, and duration) and a mechanical (MECHPA; sum of all ground reaction forces multiplied by duration) component. There were significant ethnic differences in patterns of activity. White children expended a significantly greater energy score (METPA of 21.7 +/- 2.9) than black children (METPA of 9.5 +/- 0.5) (P < 0.001). When children were divided into quartiles according to the amount and intensity of sport played, the most active white children (using METPA scores) had significantly higher whole body BMD and higher hip and spine BMC and BMD than less active children. White children in the highest MECHPA quartile also showed significantly higher whole body, hip, and spine BMC and BMD than those children in the lowest quartile. No association between exercise and bone mass of black children was found. In this population, PA has an osteogenic association with white children, but not black children, which may be explained by the lower levels of PA in the black children. Despite this, black children had significantly greater bone mass at the hip and spine (girls only) (P < 0.001) even after adjustment for body size. The role of exercise in increasing bone mass may become increasingly critical as a protective mechanism against osteoporosis in both ethnic groups, especially because the genetic benefit exhibited by black children to higher bone mass may be weakened with time, as environmental influences become stronger.

Activities of Daily Living↗

Pathological long-bone fractures in residents with cerebral palsy in a long-term care facility in South Africa.

A high incidence of long-bone fractures has been observed in children and young adults with quadriplegic cerebral palsy in residential care. This study aimed to determine factors that contribute to these fractures and to institute preventive treatment. Twenty individuals (12 males, eight females) of a cohort of 88 residents with spastic quadriplegia in residential care in Gauteng, South Africa who had sustained fractures were compared with a random sample of age-matched control participants (10 males, 10 females) from the same facility. Participants ranged in age from 6 to 29 years (median 17.5 years). The majority of fractures were in the upper extremities. There was radiological and biochemical evidence of rickets and osteomalacia in both groups. However, the severity of the disease was more pronounced in the group with fractures. There was a significant relation (p=0.002) between the number of fractures and the use of anticonvulsant therapy (ACT). Three months of vitamin D administration (calciferol 5000 iu/day) resulted in a marked clinical improvement. There were no fractures during this period in either group. In addition, the mean serum calcium (Ca) and phosphate (Pi) levels increased (Ca from 2.17 to 2.35 mmol/L and Pi from 1.13 to 1.66 mmol/L) and mean total alkaline phosphatase level decreased (from 1123 to 423 U/L). We concluded that vitamin D deficiency was the major factor contributing to the occurrence of fractures in this population. Unless sunlight exposure can be guaranteed, vitamin D supplementation should be considered for children and adults in residential care, especially if they are on ACT, even in areas with year-round sunshine.

Adolescent↗

Calcium metabolism and bone mass in female rabbits during skeletal maturation: effects of dietary calcium intake.

This study documents growth and dual-energy X-ray absorptiometry (DXA)-determined peak bone mass profiles in the rabbit model, and tests the hypothesis that rabbits show patterns of bone accretion similar to humans and thus may serve as a viable model for human bone physiology. It is also shown that dietary Ca intake affects peak bone mass and the temporal pattern of its attainment. Groups of weaned animals were administered two nutritionally complete but calcium-altered diets (0.5% or 1.0% Ca). We evaluated growth, bone mass accretion, and Ca metabolism from 20 to 56 weeks of age in both the 1.0% Ca and 0.5% Ca groups of rabbits. For each monthly period, we monitored body mass, naso-tail length, food consumption, and fecal output. In addition, we collected blood and 24 h urine samples for biochemical analyses, and measured bone mass variables of the lumbar spine with DXA. The 1.0% Ca group had a lower apparent fractional absorption of Ca and higher urinary Ca excretion, but retained more Ca than the 0.5% Ca group during the growth phase. Furthermore, the 1.0% Ca group had lower parathyroid hormone (PTH) and bone biochemical marker concentrations throughout the study than the 0.5% Ca group. The lower levels of PTH and bone markers of resorption and formation, may have resulted in a reduction in skeletal remodeling, and this physiological mechanism may have contributed to the 10% increase in peak bone mineral density of the lumbar spine in the 1.0% Ca group of rabbits.

Absorptiometry, Photon↗

Serum osteocalcin has limited usefulness as a diagnostic marker for rickets.

UNLABELLED: Serum alkaline phosphatase (AP), the bone fraction of which is secreted by osteoblasts, is elevated in rickets. Both normal and elevated levels of serum osteocalcin (OC), a bone-specific marker secreted by osteoblasts, have been reported in rickets. Expression of the OC gene is enhanced by 1,25-dihydroxyvitamin D (1,25(OH)2D) in experimental models. This study assessed serum OC levels in 14 controls and 41 patients with active rickets divided into a phosphopenic (n = 20) and a calciopenic (n = 21) group. Phosphopenic subjects were older (9.5 versus 5.7 years, P = 0.03) with higher median serum calcium level (2.35 versus 2.16 mmol/l, P = 0.0002) and serum 25-hydroxyvitamin D level (15.4 versus 10.4 ng/l, P = 0.003); and lower serum phosphate (0.80 versus 1.51 mmol/l, P = 0.0001), serum 1,25(OH)2D (43.0 versus 95.6 pg/ml, P = 0.0001) and intact serum parathyroid hormone level (45.0 versus 141.5 ng/l, P = 0.01) than calciopenic subjects. There were no differences in median serum AP (774 versus 1430 IU/l, P = 0.17) and OC (14.5 versus 13.4 ng/ml, P = 0.6) between the two groups. The mean OC value for the 41 rickets subjects was 15.1 +/- 6.2 ng/ml and 17.4 +/- 7.8 ng/ml for the 14 control subjects. In the face of markedly elevated serum AP levels in the rickets subjects, all of the serum OC values in the study fell within two standard deviations of the mean for normals. There was no association between serum OC and 1,25-(OH)2D in either the phosphopenic or the calciopenic group. CONCLUSION: These results show that serum osteocalcin levels are not elevated in all forms of active rickets and that, unlike serum alkaline phosphatase, serum osteocalcin cannot be used in the diagnosis of rickets.

Adolescent↗

Case-control study of factors associated with nutritional rickets in Nigerian children.

OBJECTIVE: Because the causes of nutritional rickets in tropical countries are poorly understood, we conducted a case-control study to determine factors associated with rickets in Nigerian children. STUDY DESIGN: We compared 123 Nigerian children who had rickets with matched control subjects. Dietary, demographic, anthropometric, and biochemical data were collected to assess factors related to calcium and vitamin D status, which might predispose children to rickets. RESULTS: Mean (+/- SD) daily dietary calcium intake was low in both children with rickets and control children (217 +/- 88 mg and 214 +/- 77 mg, respectively; P =.64). Children with rickets had a greater proportion of first-degree relatives with a history of rickets (14.6% vs 3.1%; P <.001), a shorter mean duration of breast-feeding (16.0 vs 17.3 months; P =.041), and a delayed age of walking (14 vs 12 months; P <.001). Among children with rickets, biochemical features suggestive of calcium deficiency included hypocalcemia, extremely low calcium excretion, and elevated 1, 25-dihydroxyvitamin D and parathyroid hormone values. Median 25-hydroxyvitamin D concentrations were 32 and 50 nmol/L (13 and 20 ng/mL) in children with rickets and control children, respectively (P <.0001). Only 46 subjects with rickets (37%) had 25-hydroxyvitamin D values <30 nmol/L (12 ng/mL). CONCLUSIONS: Vitamin D deficiency appears unlikely to be the primary etiologic factor of rickets in African children. Moreover, low dietary calcium intake alone does not account for rickets. Insufficient dietary calcium probably interacts with genetic, hormonal, and other nutritional factors to cause rickets in susceptible children.

Adolescent↗

Unusual presentation of congenital syphilis.

Congenital syphilis (CS) usually presents in the neonatal period and may involve any organ system. The signs are diverse and a high index of suspicion must be maintained to make the diagnosis. Early congenital syphilis can present at any time before 2 years of age, but a review of the literature over the last 30 years indicates that it usually presents in the neonatal period and seldom later than 3-4 months of life. We report an 8-month-old boy who presented an unusual combination of signs of congenital syphilis, which led to delay in establishing the diagnosis. This case emphasises the importance of maintaining a high index of suspicion for CS throughout early childhood.

Biopsy↗

Radiographic scoring method for the assessment of the severity of nutritional rickets.

Radiographic changes of rickets are well characterized, but no method of grading the severity of these changes has been in general use. Consequently, it is difficult to compare objectively or follow radiographic improvement. We prospectively evaluated the utility and reproducibility of a scoring method for measuring the severity of rickets. A 10-point score for radiographs of wrists and knees was devised to assess the degree of metaphyseal fraying and cupping and the proportion of the growth plate affected. The score progresses in half point increments from zero (normal) to 10 points (severe). Four trained physicians independently scored radiographs on two separate occasions from 67 children with active rickets. A broad representation of mean radiographic scores was moderately correlated with alkaline phosphatase (r = 0.58). Interobserver correlation of radiographic scores was 0.84 or greater for all observer pairs and intraobserver correlation was 0.89 or greater for each observer. Researchers and clinicians should find the score useful to assess objectively the severity of rickets.

Alkaline Phosphatase↗

Pediatric admissions with human immunodeficiency virus infection at a regional hospital in Soweto, South Africa.

The prevalence and clinical spectrum of HIV disease in hospitalized African children has not been adequately characterized in Southern Africa. This study aimed to determine the prevalence and disease profile of HIV infected children under 5 years of age admitted to a tertiary care hospital in Soweto, South Africa and to assess the impact of pediatric HIV on health services. Over a 6-month period, serial pediatric admissions to one of the children's wards were screened for HIV. Data on demographics and disease profile were recorded for all patients. A total of 549 patients were admitted, of whom 507 were tested for HIV; 29.2 per cent were considered to be truly infected. Previous admissions to hospital were more frequent in the HIV infected group, 48 per cent compared with 20.4 per cent of HIV uninfected children (p < 0.01), with a median length of stay of 8 days compared with 6 days (p < 0.01). There were more malnourished children in the HIV infected group (65.8 per cent compared with 33.1 per cent) (p < 0.01) and more died (17 per cent compared with 4.6 per cent) (p < 0.01). The most common reasons for admission in all children were infectious diseases such as pneumonia and gastroenteritis (85 and 31.9 per cent compared with 51 and 22.5 per cent, respectively in the HIV infected and uninfected groups, p < 0.01 and p < 0.03). It was concluded that pediatric HIV infection accounts for almost a third of childhood admissions to this hospital and has become a significant burden on the health service.

AIDS-Related Opportunistic Infections↗

Value of cerebrospinal fluid leukocyte aggregation in distinguishing the causes of meningitis in children.

BACKGROUND: Current laboratory tests often cannot distinguish between bacterial and aseptic meningitis rapidly and accurately. The ability to make a prompt diagnosis has important implications for the management and outcome of children with meningitis. The observation that leukocytes aggregate in the cerebrospinal fluid (CSF) has been previously reported, and it has been advocated as a reliable method to distinguish the causes of meningitis in children. OBJECTIVE: To investigate the utility of CSF leukocyte aggregation as a screening test to distinguish between bacterial and aseptic meningitis. METHODS: We compared the clinical and laboratory indices of 109 prospectively enrolled patients with meningitis (67 bacterial, 23 viral, 19 undefined etiology) and evaluated the validity of the CSF leukocyte aggregation test. The predefined leukocyte aggregation scores (LAS) were compared among the types of meningitis, and correlations with other markers of inflammation were calculated. RESULTS: The median LAS was significantly higher (P < 0.001) in the bacterial (32.1%; range, 0 to 84.1%) than in the viral (0%; range, 0 to 16.6%) or undefined (0%; range, 0 to 20.7%) groups. The optimal sensitivity of the leukocyte aggregation test, 98.5 to 92.5%, was demonstrated with LAS values of 0 to 3%. The corresponding specificity was 64.3 to 88.1%. The peripheral white blood cell (WBC) count, serum C-reactive protein, CSF WBC count, blood culture, CSF Gram stain and CSF culture were inferior to the LAS as screening tests when compared individually. The LAS was as effective as CSF protein, TNF-alpha, IL-1-beta, IL-6 and IL-8 to predict bacterial meningitis. In a logistic regression model that included routine laboratory tests, the best predictor of bacterial meningitis was the LAS (odds ratio, 1.6 to 3.7). Significant correlations were demonstrated between the LAS and CSF protein, CSF WBC count, IL-1-beta, IL-6 and IL-8. Duration of symptoms before diagnosis, pretreatment with antibiotics, HIV-1 infection status and CSF red blood cell count did not significantly alter the LAS. CONCLUSIONS: There is no single test to diagnose the etiology of meningitis in children promptly and accurately. The finding of leukocyte aggregation in CSF might be of value as a sensitive adjunctive screening tool for the timely diagnosis of bacterial meningitis, recognizing that it has low specificity and potential practical limitations.

Adolescent↗

Vitamin D receptor polymorphisms and nutritional rickets in Nigerian children.

Nutritional rickets is common in Nigeria where vitamin D deficiency is rare and dietary insufficiency of calcium is common. It occurs more commonly in siblings of affected children than of unaffected children. Postulating that vitamin D receptor (VDR) polymorphisms might relate to the susceptibility of some Nigerian children to develop rickets in the setting of low calcium intake, we compared the VDR genotypes, as determined by the presence or absence of Bsm I, Apa I, Taq I, and Fok I restriction enzyme cleavage sites, between 105 children with active nutritional rickets and 94 subjects representative of the community from which the rachitic children came. In the rickets group, the ff genotype was less common than in the community group, and the FF genotype was relatively increased (f allele frequency, 17% in rachitic children and 26% in the community group, p = 0.03). Neither individual allele frequencies for the other polymorphisms nor combinations of genotypes at different sites were different between the rachitic and community groups. Although it is not clear why a presumed better-functioning VDR variant (F allele) is associated with an increased risk of developing rickets, this study raises the possibility that VDR alleles might be important in determining an individual's susceptibility to developing rickets when faced with dietary calcium deficiency.

Adult↗

Validation and application of dual-energy X-ray absorptiometry to measure bone mineral density in rabbit vertebrae.

The rabbit could be a superior animal model to use in bone physiology studies, for the rabbit does attain true skeletal maturity. However, there are neither normative bone mineral density (BMD) data on the rabbit nor are there any validation studies on the use of dual-energy X-ray absorptiometry (DXA) to measure spinal BMD in the rabbit. Therefore, our aim was twofold: first, to investigate whether DXA could be used precisely and accurately to determine the bone mineral content (BMC). bone area (BA). and BMD of the rabbit lumbar spine: Second. to evaluate the new generation fan-beam DXA (Hologic QDR-4500) with small animal software by comparing two DXA methodologies QDR-1000 and QDR-4500 with each other, as well as against volumetric bone density (VBMD) derived from Archimedes principle. As expected. there was a magnification error in the QDR-4500 (BMC, BA. and BMD increased by 52%. 38%. and 10%, respectively, when the vertebrae were positioned flat against the scanning table). With the magnification error kept constant (vertebrae positioned 10 cm above the scanning table to match the height in vivo). there were no differences among the mean BMC. BA. and BMD of the rabbit vertebrae (Ll-L7) in vivo and in vitro using the QDR-4500 (p > 0.05). BMC, BA, and BMD differed between QDR-1000 and QDR-4500 in vitro because of a magnification error when the vertebrae were flat on the table (p <0.0001). and, consequently. the machines did not correlate with one another (p > 0.05). However, the BMC, BA, and BMD of the two DXAs did significantly correlate with each other in vivo and in vitro when the magnification error was compensated for (r = 0.44 and 0.52. i2 = 0.45 and 0.63. and 12 = 0.41 and 0.60. respectively. p < 0.05-0.008). The BMC and BMD (in vivo and in vitro) of the rabbit vertebrae measured by QDR-4500 was significantly correlated with VMBD, ash weight, and mineral content (,2 = 0.67-0.90,j <0.01-0.0001). Therefore, the QDR-4500 can be used to yield precise and accurate measurements of the rabbit spine.

Absorptiometry, Photon↗

A comparison of calcium, vitamin D, or both for nutritional rickets in Nigerian children.

BACKGROUND: Nutritional rickets remains prevalent in many tropical countries despite the fact that such countries have ample sunlight. Some postulate that a deficiency of dietary calcium, rather than vitamin D, is often responsible for rickets after infancy. METHODS: We enrolled 123 Nigerian children (median age, 46 months) with rickets in a randomized, double-blind, controlled trial of 24 weeks of treatment with vitamin D (600,000 U intramuscularly at enrollment and at 12 weeks), calcium (1000 mg daily), or a combination of vitamin D and calcium. We compared the calcium intake of the children at enrollment with that of control children without rickets who were matched for sex, age, and weight. We measured serum calcium and alkaline phosphatase and used a 10-point radiographic score to assess the response to treatment at 24 weeks. RESULTS: The daily dietary calcium intake was low in the children with rickets and the control children (median, 203 mg and 196 mg, respectively; P=0.64). Treatment produced a smaller increase in the mean (+/-SD) serum calcium concentration in the vitamin D group (from 7.8+/-0.8 mg per deciliter [2.0+/-0.2 mmol per liter] at base line to 8.3+/-0.7 mg per deciliter [2.1+/-0.2 mmol per liter] at 24 weeks) than in the calcium group (from 7.5+/-0.8 [1.9+/-0.2 mmol per liter] to 9.0+/-0.6 mg per deciliter [2.2+/-0.2 mmol per liter], P<0.001) or the combination-therapy group (from 7.7+/-1.0 [1.9+/-0.25 mmol per liter] to 9.1+/-0.6 mg per deciliter [2.3+/-0.2 mmol per liter], P<0.001). A greater proportion of children in the calcium and combination-therapy groups than in the vitamin D group reached the combined end point of a serum alkaline phosphatase concentration of 350 U per liter or less and radiographic evidence of nearly complete healing of rickets (61 percent, 58 percent, and 19 percent, respectively; P<0.001). CONCLUSIONS: Nigerian children with rickets have a low intake of calcium and have a better response to treatment with calcium alone or in combination with vitamin D than to treatment with vitamin D alone.

Alkaline Phosphatase↗

Paediatric hospital admissions at a South African urban regional hospital: the impact of HIV, 1992-1997.

Rates of infection by the human immunodeficiency virus (HIV) have been increasing rapidly in South Africa over the last decade. This study documents the changes over time in prevalence of HIV infection amongst hospitalized children, and its effects on the profile of disease and in-hospital mortality over the period 1992-1997. Admissions to the paediatric medical wards between January 1992 and April 1997 were obtained from the routine computerized database held in the Department of Paediatrics at Chris Hani Baragwanath Hospital. HIV tests were performed on clinical indications only. Over the study period there were 22,633 admissions involving 19,918 children. Total annual admissions increased by 23.6% between 1992 and 1996. Prevalence of HIV infection increased from 2.9% in 1992 to 20% in 1997. HIV-infected children had a younger age distribution, longer median length of stay and more readmissions (p < 0.001) compared with HIV-negative and untested children. HIV-infected children accounted for the increased number of admissions for pneumonia, gastro-enteritis, malnutrition and tuberculosis, and the rise in in-hospital mortality by 42% from 4.3% in 1992 to 6.1% in 1997. Paediatric HIV infection has changed the profile of paediatric admission diagnoses and increased in-hospital mortality in the relatively short time between 1992 and 1997. Over the same period, HIV-negative children showed declining rates of malnutrition, vaccine-preventable diseases and admission to the intensive care unit.

AIDS-Related Opportunistic Infections↗

Correlation between CD4+ lymphocyte counts, concurrent antigen skin test and tuberculin skin test reactivity in human immunodeficiency virus type 1-infected and -uninfected children with tuberculosis.

BACKGROUND: HIV-infected children are at high risk of developing tuberculosis after infection by Mycobacterium tuberculosis. Emphasis is placed on tuberculin skin testing (TST) for diagnosing tuberculosis in children; however, its value in HIV-infected children is controversial. OBJECTIVES: To determine whether concurrent antigen testing and/or CD4+ lymphocyte counts help in the interpretation of the TST in children with tuberculosis. METHODS: Children eligible for the study were diagnosed as having tuberculosis on clinical criteria. CD4+ lymphocyte counts and delayed-type hypersensitivity (DTH) test, using the CMI Multitest were performed when tuberculosis was diagnosed. RESULTS: One hundred thirty children were enrolled. Tuberculin reactivity was lower in HIV-infected children at all cutoff levels than in HIV-uninfected children (P < 0.0001). The positive predictive value of normal CD4+ lymphocyte counts in predicting tuberculin reactions of > or =5 mm (in HIV-1-infected) and > or =10 mm (in HIV-uninfected patients) were 50 and 80.3%, respectively (P < 0.0001). An intact DTH reaction to the CMI Multitest in predicting reactions of > or =5 mm and > or =10 mm to tuberculin in HIV-infected and -uninfected children were 55 and 76%, respectively (P < 0.001). Kwashiorkor was responsible for 53.3% of false-negative TST in HIV-uninfected children with normal CD4+ lymphocyte counts. CONCLUSION: TST is of limited value as an adjunct in diagnosing tuberculosis in HIV-infected children. CD4+ lymphocyte counts and concurrent DTH testing are not useful for predicting tuberculin reactivity in HIV-infected patients with tuberculosis.

AIDS-Related Opportunistic Infections↗