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Biomedical subjects

S F Ahmed

Publications and source records attributed to S F Ahmed.

At least 19 recordsLinked to original sources
PubMed2006

The growth plate sparing effects of the selective glucocorticoid receptor modulator, AL-438.

Long-term use of glucocorticoids (GC) can cause growth retardation in children due to their actions on growth plate chondrocytes. AL-438, a non-steroidal anti-inflammatory agent that acts through the glucocorticoid receptor (GR) retains full anti-inflammatory efficacy but has reduced negative effects on osteoblasts compared to those elicited by prednisolone (Pred) or dexamethasone (Dex). We have used the murine chondrogenic ATDC5 cell line to compare the effects of AL-438 with those of Dex and Pred on chondrocyte dynamics. Dex and Pred caused a reduction in cell proliferation and proteoglycan synthesis, whereas exposure to AL-438 had no effect. LPS-induced IL-6 production in ATDC5 cells was reduced by Dex or AL-438, showing that AL-438 has similar anti-inflammatory efficacy to Dex in these cells. Fetal mouse metatarsals grown in the presence of Dex were shorter than control bones whereas AL-438 treated metatarsals paralleled control bone growth. These results indicate that the adverse effects Dex or Pred have on chondrocyte proliferation and bone growth were attenuated following AL-438 exposure, suggesting that AL-438 has a reduced side effect profile on chondrocytes compared to other GCs. This could prove important in the search for new anti-inflammatory treatments for children.

Animals↗
PubMed2006

Epidemiology and genetic characterization of Shigella flexneri strains isolated from three paediatric populations in Egypt (2000-2004).

Ninety-seven isolates of Shigella flexneri from children seeking medical care from three sites in Egypt were characterized. Overall, 46.4% of children (median age 17 months) were febrile or reported blood in their stools, 25.8% were dehydrated and 16.5% were admitted to hospital. Serotypes 2a (37.1%), 1b (18.6%), 1c (17.5%), and 6 (15.5%) comprised over 88.7% of the total isolates. We observed marked resistance to ampicillin (87.6%), tetracycline (84.5%) and trimethoprim-sulfamethoxazole (63.9%). Pulsed-field electrophoresis grouped the majority of isolates within a serotype together, separately from isolates of an alternative serotype. The set gene was present in all serogroup 2a isolates, however, the sen gene was detected in every isolate. Our results show S. flexneri 1c has emerged as a dominant S. flexneri serotype in Egypt. Development and application of a Shigella vaccine should consider the diversity of Shigella serotypes within a geographical region prior to administration.

Anti-Bacterial Agents↗
PubMed2006

Longitudinal changes in bone health as assessed by the speed of sound in very low birth weight preterm infants.

OBJECTIVE: To assess longitudinal changes in speed of sound (SOS) in very low birth weight (VLBW) infants and investigate the relationship with markers of osteopathy of prematurity (OP) and clinical illness. STUDY DESIGN: Twenty-five infants were recruited. Eighteen infants, median gestation 27 weeks (range 24-32), median birth weight 957 g (range 625-1500 g), had serial scans. SOS was measured at both tibiae weekly until 35 to 37 weeks corrected gestational age (CGA). RESULTS: Initial median SOS standard deviation score (SDS) (Z) score was -0.07 (range-1.3-1.3). SOS correlated with gestation (r, 0.8, P<.005), and birth weight (r, 0.67, P<.005.) SOS fell from a median of 2923 m/s (2672-3107) at birth to 2802 m/s (2502-2991) at 35 to 37 weeks CGA (P<.05). This fall was greater in the 24- to 27-week gestation cohort with a median reduction of 2.2 SDS (1.6, 4.0) compared with 1.3 SDS (0.8-2.2) in those>28 weeks (P<.05). There was a negative correlation between SOS, at the end of the study, peak serum alkaline phosphatase (ALP) (r, 0.6, P<.05), CRIB (Clinical Risk Index for Babies)/CRIB II scores (both r, 0.6, P<.05), and duration of total parenteral nutrition (TPN) (r, 0.58, P<.05.) CONCLUSIONS: Although tibial SOS was within the expected range at birth, there was a subsequent failure to gain SOS, and this was most marked in infants of a lower gestation.

Alkaline Phosphatase↗
PubMed2006

The role of pro-inflammatory cytokines in inflammatory bowel disease growth retardation.

Childhood inflammatory bowel disease (IBD) especially those with Crohn disease is commonly complicated by faltering growth and pubertal delay. Pro-inflammatory cytokines are often elevated in IBD and may affect linear growth and puberty either systemically or at the level of the growth plate. Further study of the underlying mechanisms of the deleterious effects of cytokines on the growth plate may improve management of faltering growth in childhood IBD. Well-controlled clinical studies of the respective effect of nutritional support, immunomodulatory therapy, biological agents and growth and puberty promoting agents on managing faltering growth also require further attention.

Adolescent↗
PubMed2006

Undetectable salivary testosterone in young women with premature ovarian failure.

BACKGROUND: The extent of androgen deficiency in young women with premature ovarian failure (POF) is unclear. AIM: Cross-sectional study of androgen status in young women with POF. PATIENTS: Twenty women with POF: six had Turner syndrome (group A); eight had iatrogenic POF either secondary to bilateral oophorectomy or treatment of malignancy (group B); and six had idiopathic POF (group C). The median age was 30.5 years (range 19-39); in groups B and C the median duration of ovarian failure was 10.0 years (range 1-35). METHODS: After a 2-month wash-out period without sex steroid replacement (SSR), serum testosterone (T), androstenedione (A4), dehydroepiandrosterone (DHEAS), SHBG, salivary testosterone (SalT) and the free androgen index [FAI = (serum T/SHBG) x 100] were measured. RESULTS: Median serum A4 was 4.6 nmol/l (10th, 90th centiles, 3.6, 5.1) and DHEAS was 3.2 micromol/l (10th, 90th centiles, 2.3, 9.3). Although median serum T was relatively low at 1.4 nmol/l (10th, 90th centiles, 1.1, 1.7), median SHBG was also low at 34 nmol/l (10th, 90th centiles 22.2, 67.5) and the median calculated FAI was within the normal range at 3.7 (10th, 90th centiles, 2.3, 7.0). However, SalT was undetectable in almost all subjects in the three groups of POF. CONCLUSIONS: Serum T and SHBG are relatively low in young women with POF and their FAI is therefore within the normal range. However, SalT, which measures free testosterone, is consistently low to undetectable in these young women with POF. The reliability of the FAI as a marker of androgen deficiency remains questionable.

Adult↗
PubMed2006

Biliary hypoplasia in Williams syndrome.

Neonatal hepatitis and biliary hypoplasia are not recognised features of Williams syndrome. A case of Williams syndrome, presenting with neonatal conjugated hyperbilirubinaemia leading to an initial misdiagnosis is reported.

Alagille Syndrome↗
PubMed2006

The restricted potential for recovery of growth plate chondrogenesis and longitudinal bone growth following exposure to pro-inflammatory cytokines.

Childhood chronic inflammatory disease can be associated with transient and permanent growth retardation. This study examined the potential for spontaneous growth recovery following pro-inflammatory cytokine exposure. Murine ATDC5 chondrogenic cells and postnatal metatarsals were exposed to interleukin (IL)-1beta, IL-6 and tumour necrosis factor-alpha (TNFalpha), and their growth and proliferative capacity were determined following recovery. TNFalpha and IL-1beta reduced chondrocyte proliferation and aggrecan and collagen types II and X expression at minimum concentrations of 10 ng/ml and 0.1 ng/ml respectively. TNFalpha but not IL-1beta exposure led to increased caspase-3 activity and altered cellular morphology, consistent with reduced viability. Cytokine exposure particularly inhibited proteoglycan synthesis. This effect was dose and duration dependent. Compared with the control, IL-1beta and TNFalpha led to a 71% and 45% reduction in metatarsal growth after 8 days of exposure respectively (P < 0.05). An additive effect of IL-1beta combined with TNFalpha was observed (110% decrease; P < 0.05). Metatarsals exposed to IL-1beta or TNFalpha individually for a 2-day period, and allowed to recover spontaneously in the absence of cytokines for a further 6 days, showed normal growth trajectories. In combination, growth was 59% lower (P < 0.01) compared with control metatarsals at the end of the recovery period. Exposure to the combination for 4 days followed by a 4-day recovery period resulted in 87% decrement compared with controls (P < 0.05). IL-6 did not alter any parameter studied. IL-1beta and TNFalpha exert diverse inhibitory effects on ATDC5 chondrocyte dynamics and metatarsal growth. The extent of recovery following cytokine exposure depends on the duration of exposure, and may be incomplete following longer periods of exposure.

Animals↗
PubMed2006

Ceramide inhibition of chondrocyte proliferation and bone growth is IGF-I independent.

Proinflammatory cytokines inhibit growth plate development. However, their underlying mechanisms of action are unclear. These effects may be mediated by ceramide, a sphingosine-based lipid second messenger, which is elevated in a number of chronic inflammatory diseases. To test this hypothesis, we determined the effects of C2-ceramide, a cell permeable ceramide analogue, on the growth of the ATDC5 chondrogenic cell line and on cultured fetal mice metatarsals. In ATDC5 cells, C2-ceramide significantly induced apoptosis at both 40 (82%; P < 0.05) and 25 microM (53%; P < 0.05). At 40 microM, C2-ceramide significantly reduced proliferation ([3H]-thymidine uptake/mg protein) (62%; P < 0.05). C2-ceramide did not markedly alter the differentiation state of the cells as judged by the expression of markers of chondrogenesis and differentiation (sox 9, collagen II and collagen X). The IGF-I signalling pathway is the major autocrine/paracrine regulator of bone growth. Both in the presence and absence of IGF-I, C2-ceramide (25 microM) induced an equivalent reduction in proliferation (60%; P < 0.001). Similarly, C2-ceramide (40 microM) induced a 31% reduction in fetal metatarsal growth both in the presence and absence of IGF-I (both P < 0.001). Furthermore, C2-ceramide reduced ADCT5 proliferation in the presence of AG1024, an IGF-I and insulin receptor blocker. Therefore, C2-ceramide-dependent inhibition appears to be independent of IGF-mediated stimulation of bone growth. Indeed, biochemical studies demonstrated that C2-ceramide (25 microM) pretreatment did not alter IGF-I-stimulated phosphorylation of insulin receptor substrate-1, Akt or P44/42 MAP kinase. In conclusion, C2-ceramide inhibits proliferation and induces apoptosis in growth plate chondrocytes through an IGF-I independent mechanism.

Animals↗
PubMed2006

Cytokine actions in growth disorders associated with pediatric chronic inflammatory diseases (review).

Growth disorders are commonly observed in children suffering from chronic inflammatory diseases such as Juvenile Idiopathic Arthritis (JIA) and Inflammatory Bowel Disease (IBD). These disorders range from general growth retardation to local acceleration of growth in the affected limb and are associated with the increased production of pro-inflammatory cytokines. In this article, we review how cytokines influence child growth by exerting a local effect at the level of the growth plate, and through systemic effects throughout the whole body.

Arthritis, Juvenile↗
PubMed2005

The pathophysiology of the growth plate in juvenile idiopathic arthritis.

Children with chronic inflammatory diseases, such as juvenile idiopathic arthritis (JIA), suffer from a variety of growth disorders. These range from general growth retardation to local acceleration of growth in the affected limb. These disorders are associated with the increased production of proinflammatory cytokines, which may influence growth through a local effect in the growth plates of long bones and/or systemic effects throughout the whole body. In this article we review these aspects and also discuss the evidence for interaction between the inflammatory cytokine and growth-signalling pathways.

Arthritis, Juvenile↗
PubMed2005

Quantitative ultrasound assessment of bone in preterm and term neonates.

There is a need to explore novel methods of assessing bone health in sick preterm infants. This study of the speed of sound in the long bones of newborn term and preterm infants shows that, in this population, this technique is not site specific and has a high degree of interobserver and intraobserver precision. The speed of sound in newborn infants is primarily dependent on gestation rather than birth weight.

Birth Weight↗
PubMed2004

Insulin-like growth factor-I augments chondrocyte hypertrophy and reverses glucocorticoid-mediated growth retardation in fetal mice metatarsal cultures.

The study aims were to improve our understanding of the mechanisms of glucocorticoid-induced growth retardation at the growth plate and determine whether IGF-I could ameliorate the effects. Fetal mouse metatarsals were cultured for up to 10 d with dexamethasone (Dex; 10(-6) m) and/or IGF-I and GH (both at 100 ng/ml). Both continuous and alternate-day Dex treatment inhibited bone growth to a similar degree, whereas IGF-I alone or together with Dex caused an increase in bone growth. GH had no effects. These observations may be explained at the cellular level; cell proliferation within the growing bone was decreased by Dex and increased by IGF-I and these effects were more marked in the cells of the perichondrium than those in the growth plate. However, the most prominent observation was noted in the hypertrophic zone where all treatments containing IGF-I significantly increased (3-fold) the length of this zone, whereas Dex alone had no significant effect. In conclusion, Dex impaired longitudinal growth by inhibiting chondrocyte proliferation, whereas IGF-I stimulated chondrocyte hypertrophy and reversed the growth-inhibitory Dex effects. However, the IGF-I-mediated improvement in growth was at the expense of altering the balance between proliferating and hypertrophic chondrocytes within the metatarsal.

Alkaline Phosphatase↗
PubMed2004

Bone mineral assessment by dual energy X-ray absorptiometry in children with inflammatory bowel disease: evaluation by age or bone area.

BACKGROUND: Abnormal linear growth and deficient bone mineral acquisition may coexist in children with inflammatory bowel disease (IBD). Traditionally, bone mineral assessment by dual energy x-ray absorptiometry (DXA) involves comparison to age- and gender-matched reference ranges, and these studies in children with IBD show a high prevalence of osteopenia. AIMS: To compare the prevalence of osteopenia using two methods of interpretation; one adjusted for age and gender and the other adjusted for bone size and gender. PATIENTS: Forty-seven patients with Crohn disease (CD) and 26 patients with ulcerative colitis (UC) with a median age of 13.5 years (range, 5.5-18.2 years) were evaluated. METHODS: Lumbar spine (LS) and total body (TB) bone mineral content (BMC) were measured by DXA and converted to bone mineral density (BMD, g/cm) corresponding to BMC divided by the bone area. Age and gender-matched BMD standard deviation scores (SDS) were based on reference data providing age- and gender-matched BMC and bone area. These data also allowed calculation of percentage of predicted bone area for age and gender (ppBone Area) and percentage of predicted BMC for Bone Area (ppBMC). RESULTS: Patients with CD were shorter than those with UC (median height, SDS, -0.9 v 0, P < 0.05). Median ppBone Area for LS and TB for the whole group was 85% (10th centile, 68; 90th centile 99) and 81% (10th centile 66; 90th centile, 97), respectively. The ppBone Area at both sites was directly related to height SDS and BMI SDS (r > 0.5; P < 0.005). Median BMD SDS for LS and TB was -1.6 (10th centile -3.6; 90th centile, -0.2) and -0.9 (10th centile, -2.4; 90th centile, 0.4), respectively. Median ppBMC for LS and TB was 98% (10th centile, 84%; 90th centile, 113%) and 101% (10th centile 94%; 90th centile, 107%), respectively. The ppBMC showed no relationship to ppBone Area (r = 0.1, NS). Failure to account for bone area led to a label of moderate or severe osteopenia in 65% of cases. After adjustment for bone area, the proportion of children with osteopenia fell to 22%. CONCLUSIONS: The data suggest that children with IBD often have small bones for age because they have growth retardation. When DXA data are interpreted with adjustment for bone size, most children were found to have adequate bone mass. Correct interpretation of DXA is important for identifying children who may be at a real risk of osteoporosis.

Absorptiometry, Photon↗
PubMed2004

Prevalence of hypospadias and other genital anomalies among singleton births, 1988-1997, in Scotland.

BACKGROUND: Considerable debate exists on the epidemiology of genital anomalies. METHODS: All genital anomalies, excluding undescended testes, were identified from neonatal returns, stillbirth and infant death survey records, and returns relating to hospital admissions and linked to form infant profiles on a cohort of singleton births between 1988 and 1997 with follow up for a minimum of three years. FINDINGS: The mean genital anomaly prevalence rate in Scotland was calculated at 4.6 per 1000 births varying from 4.0 per 1000 births in 1988 to 5.9 per 1000 births in 1996. However, there was no evidence of a clear trend to an increasing prevalence of hypospadias, which constituted 73% of the anomalies studied. Logistic regression analysis of the data also showed this rate to be independently associated with being relatively small for gestational age (odds ratio (OR) 1.43, p < 0.001) and increasing maternal age (OR 1.2, p < 0.05). Infants born in deprived areas, as judged by the Carstairs deprivation score, were least likely to have a genital anomaly (OR 0.73, p < 0.01). INTERPRETATION: A new linked register of congenital genital anomalies in Scotland suggests that over a decade, the birth prevalence of genital anomalies has changed little. The associations between genital anomalies, maternal age, and socioeconomic deprivation require further study.

Cohort Studies↗
PubMed2004

Testosterone measurements in early infancy.

Circulating testosterone concentrations in infants measured by a direct chemiluminescent immunoassay (Bayer ADVIA Centaur) were compared with those measured by a traditional radioimmunoassay using solvent extraction. The results confirm that neonatal circulating testosterone concentrations are method dependent, and each laboratory should establish method related reference ranges especially if using a direct commercial immunoassay. The results indicate that the Bayer ADVIA Centaur procedure can be used reliably in neonates. Expected values for male and female infants < 10 days old were 2.5-11.1 (n = 36) and 1.7-5.6 (n = 36) nmol/l respectively. For older neonates (10-50 days) the ranges were 0.2-17.2 (n = 42) and 0.1-1.5 (n = 7) nmol/l respectively.

Age Factors↗
PubMed2004

Intersex and gender assignment; the third way?

The birth of a new baby is one of the greatest wonders of nature and one of the most exciting events known to man. The first question that is usually posed by the mother or father is "is it a boy or a girl?"; without this information the new parents cannot even formulate the second question which is usually "is he/she alright?". It is no wonder that the birth of a child with complex genital anomalies where the sex of rearing is uncertain at birth, presents difficult clinical and ethical issues.

Attitude to Health↗