Growth of Pakistani children in relation to the 1990 growth standards

This study was designed to compare the growth of Pakistani schoolchildren in the UK with the 1990 UK growth standards. Measurements of height, weight, and sitting height were performed on 785 Pakistani schoolchildren aged 5-14 years with the mean values for each age and sex being plotted on the UK growth standards. The results were expressed as SD scores relative to the 1990 reference data. The mean height for the boys was only 0.2 SD scores below the mean for the new growth standards with the mean height for the girls being 0.4 SD scores below the mean. The mean values for weight and body mass index were 0.3 and 0.5 SD scores less than the mean for boys and girls respectively. This study demonstrates that the growth of Pakistani schoolchildren in the UK is comparable to the 1990 UK growth standards with only minor differences. It is not safe to assume that short stature or low body weight in a Pakistani child is due to his or her ethnic background.     

Hormone replacement therapy with dydrogesterone and 17β-oestradiol: effects on serum lipoproteins and glucose tolerance during 24 month follow up

Objective To assess serum lipid and lipoprotein concentrations and oral glucose tolerance in postmenopausal women treated with 17β-oestradiol (2 mg/day) and cyclical dydrogesterone (10 mg/day for 14 days per 28 day cycle).
Design A 24 month prospective study of 29 women acting as their own controls. On-treatment samples were taken during the combined (oestrogen–progestogen) phase of therapy.
Setting Metabolic research unit in London.
Population Postmenopausal women with no previous exposure to hormone replacement therapy attending a menopause clinic in a London hospital.
Methods Fasting serum sampling and oral glucose tolerance testing.
Main outcome measures Serum lipids and lipoprotein concentrations and plasma glucose, insulin and C-peptide responses to an oral glucose load.
Results Restricting the analysis to the 17 women who completed the study, no effect was seen on serum triglyceride concentrations. There was a mean fall of 5.9% (95% CI 1.2 to −13.0) in concentrations of serum total cholesterol, reflecting the balance of a 10.7% fall (95% CI 4.3 to −25.8) in low density lipoprotein cholesterol concentrations and a 16.3% increase (95% CI 7.3 to −25.3) in those of high density lipoproteins. Fasting glucose concentrations and glucose tolerance test responses were unchanged. Fasting insulin concentrations fell substantially (–41.6%, 95% CI −23.4 to −59.8) with falls also being seen in insulin responses to glucose. Fasting C-peptide concentrations increased by 36.2% (95% CI 9.17 to 63.3), with no consistent effect on C-peptide responses to glucose.
Conclusions Dydrogesterone did not appear to oppose the potentially beneficial effects of oestradiol on insulin or either low or high density lipoproteins, making the combination with 17β-oestradiol a potentially useful option for postmenopausal women particularly those at risk of cardiovascular disease or diabetes mellitus.     

Fatty acid balance studies in term infants fed formula milk containing long-chain polyunsaturated fatty acids

Long-chain polyunsaturated fatty acids (LCP) are thought to be required for optimal nervous system development in the newborn. A commercial milk formula containing LCP (Aptamil-LCP) with a fatty acid profile closely resembling breast milk, has recently been introduced for term infants. The absorption of fatty acids in term infants was examined in a double-blind randomized controlled trial comparing Aptamil-LCP ( n = 20) and standard Aptamil ( n = 20). Formula-fed newborn infants were studied from birth for 14 d. Fat balances (3 d) were performed from d 10. A 3-d stool collection was performed from d 10 in a parallel breastfed group ( n = 21). Plasma samples were taken on d 6. Median fat excretion (mg kg⁻¹) was 897.1, 615.0 and 355.2 with Aptamil, Aptamil-LCP and breastfeeding, respectively. The median total fat absorption coefficient in Aptamil-LCP-fed infants was higher than in those fed standard Aptamil ( p < 0:01). These findings were accounted for by differences in the excretion and absorption of long-chain saturated fatty acids (C14:0, C16:0 and C18:0). Higher fat excretion was associated with bulkier and firmer stools. Only trace amounts of LCP were detected in the stools of all groups. This accounted for less than 4% of dietary intake in Aptamil-LCP-fed infants. No differences in the utilization of LCP from Aptamil-LCP and breast milk feeding were apparent. Plasma phospholipid fatty acid composition data reflected differences in dietary LCP intake. Thus, PL LCP levels were highest in the breastfed infants and lowest in the Aptamil-fed infants, with values for the Aptamil-LCP-fed group falling in between.     

Adaptive response of human melanoma cells to methylglyoxal injury

The effects of methylglyoxal on the growth of a line of human melanoma cells are investigated. Methylglyoxal inhibits cell growth in a dose- dependent manner and causes an increase in glyceraldehyde 3-phosphate dehydrogenase, and glyoxalase 1 and glyoxalase 2 specific activities. The cellular response to increasing concentrations of methylglyoxal in the culture medium is also studied by measuring L-lactate production, reduced-oxidized glutathione levels and apoptotic cell death. Methylglyoxal seems to promote a change of cell population phenotypic repertoire toward a more monomorphic phenotype. In conclusion, methylglyoxal seems to induce an enzymatic cellular response that lowers methylglyoxal levels and selects the most resistant cells.      

The effect of non-genotoxic carcinogens, phenobarbital and clofibrate, on the relationship between reactive oxygen species, antioxidant enzyme expression and apoptosis

Phenobarbital and clofibrate, two non-genotoxic carcinogens, have been investigated regarding the relationship between reactive oxygen species, antioxidant enzyme expression and apoptosis in primary cultures of rat hepatocytes. Low toxicity concentrations, 200 and 100 microg/ml for phenobarbital and clofibrate respectively, were used to examine their effect on spontaneous or transforming growth factor beta1 (TGFbeta1)-induced apoptosis and on the expression of antioxidant defence enzymes (superoxide dismutases and catalase). The increased incidence of apoptotic nuclei was visualized in TGFbeta1-treated cultures with the fluorescent dye Hoechst 33258 and was quantified under all experimental conditions by measurement of the hypodiploid peak in DNA histograms obtained by flow cytometry. Both substances, when added separately to hepatocyte cultures and incubated for 24 and 48 h, significantly diminished spontaneous apoptosis and exhibited a slight suppression of TGFbeta1-induced apoptosis. Endogenous peroxide production by hepatocytes increased with TGFbeta1, phenobarbital or clofibrate and the increase was greater with phenobarbital and in the presence of TGFbeta1 with both drugs. Gene expression of catalase and Mn- and Cu,Zn superoxide dismutases (SOD) was evaluated by northern blot analysis of hepatocytes incubated in the presence of phenobarbital or clofibrate with or without TGFbeta1 and the following differences were detected: phenobarbital induced a significant decrease in both dismutases (to 56%, P < 0.05, and 55%, P < 0.05, for Mn- and Cu,Zn-SOD respectively) and a 2-fold increase (P < 0.01) in catalase; clofibrate induced a slight decrease in both SODs and a 4-fold increase (P < 0.05) in catalase; TGFbeta1 significantly decreased to 37% (P < 0.05) expression of catalase while not significantly affecting expression of both SODs. We conclude that inhibition of spontaneous apoptosis induced by either phenobarbital or clofibrate is accompanied by increases in the endogenous levels of peroxides and by significant induction of catalase gene expression. Furthermore, the lack of effect of both compounds on TGFbeta1-induced apoptosis could be a consequence of the inability of these two compounds to counteract the depressing effect of TGFbeta1 on expression of catalase.      

The constitutive secretory pathway is a major route for islet amyloid polypeptide secretion in neonatal but not adult rat islet cells

Islet amyloid polypeptide (IAPP or amylin) is a normal secretory product of the pancreatic beta-cell that is cosecreted with insulin and is the major constituent of islet amyloid deposits in individuals with type 2 diabetes or insulinomas. We have previously reported that glucose stimulates IAPP, but not insulin secretion, from neonatal rat beta-cells when regulated secretion is prevented by use of calcium-free media, suggesting that IAPP secretion occurs via a constitutive secretory pathway. To directly test this hypothesis, we examined the effects of 2 substances-brefeldin A (BFA) and cycloheximide (CHX)-that are predicted to selectively block constitutive secretion on the release of IAPP-like immunoreactivity (IAPP-LI) and immunoreactive insulin (IRI) from neonatal rat islet cell monolayer cultures. When regulated release was prevented by use of calcium-free media, glucose-stimulated IAPP-LI release was nearly abolished by blocking constitutive release with 10 microg/ml BFA (mean +/- SD: 8.7 +/- 7.7 vs. 29.3 +/- 14.3 pmol/l; n = 5; P < 0.05), an inhibitor of constitutive vesicle formation. Similarly, calcium-independent, glucose-stimulated IAPP-LI secretion was markedly suppressed when new protein synthesis was blocked by administration of 20 microg/ml CHX (4.6 +/- 2.1 vs. 29.5 +/- 14.0 pmol/l; n = 5; P < 0.005). Secretion of IRI was low in the absence of calcium, and neither BFA nor CHX had any further effect. When calcium was added to the incubation media to allow regulated secretion of both IRI and IAPP-LI, both BFA (47.7 micro 8.7 vs. 80.7 micro 10.3 pmol/l; P < 0.001) and CHX (37.3 +/- 5.8 vs. 73.3 +/- 6.2 pmol/l; n = 5; P < 0.0001) inhibited glucose-stimulated IAPP-LI secretion by approximately 40%, but again had no inhibitory effect on IRI secretion. These data indicate that approximately 40% of glucose-stimulated IAPP-LI release occurs via a constitutive secretory pathway in neonatal rat islet cells. By contrast, in adult rat islets, glucose-stimulated IAPP-LI release was almost abolished in the absence of calcium (86 +/- 3% inhibition; P < 0.05) and unaffected by addition of BFA (275 +/- 28 vs. 205 +/- 89 pmol/l; NS) or CHX (160 +/- 20 vs. 205 +/- 89 pmol/l; NS), suggesting that constitutive secretion of IAPP does not occur in mature beta-cells. Collectively, these data suggest that a significant proportion of glucose-stimulated IAPP secretion from neonatal, but not adult, rat islet cells occurs via a constitutive secretory pathway.     

The changing face of gastroschisis and omphalocele in southeast Georgia.

OBJECTIVE: To document trends in the clinical characteristics of gastroschisis and omphalocele in southeast Georgia, USA, from 1994 to 2002. METHODS: All babies with an abdominal wall defect in a 19-county region were referred to one Perinatal Center for genetic counseling, level II ultrasound scans, pregnancy follow-up and delivery. Karyotyping was offered for omphalocele, advanced maternal age, family history predisposing to aneuploidy, and gastroschisis with an additional anomaly. RESULTS: There were 64 patients, 34 with gastroschisis and 30 with omphalocele. From 1994 to 2002, the birth prevalence of gastroschisis was 1:3600 and omphalocele 1:3400, but from 2000 to 2002, gastroschisis increased to 1:1667, while omphalocele increased to only 1:2709. Gender distribution was different: for gastroschisis the M:F ratio was 1:2.1; for omphalocele the ratio was 1.7:1. In the patients with omphalocele, 90% had an amniocentesis and 9/27 were aneuploid: five had trisomy 18, three had trisomy 13 and one had trisomy 21. Seventy-six per cent of the patients with omphalocele had associated anomalies, but only 17.6% of those with gastroschisis. Mothers whose babies had gastroschisis showed a trend to progressively younger age, while no such trend was observed among mothers whose babies had omphalocele. CONCLUSION: The birth prevalence of abdominal wall defects in general is increasing, but more notably for gastroschisis. Maternal age continues to decrease for gastroschisis. In the study population, gender distribution showed a statistically significant variation between the defects.     

Rendu–Osler–Weber syndrome presenting with pulmonary arteriovenous fistula

A pulmonary arteriovenous fistula is an abnormal connection between pulmonary arteries and veins. Patients with Rendu–Osler–Weber syndrome may present with this vascular malformation, which is a typical finding of the disease. Approximately 5–15% of Rendu–Osler–Weber syndrome patients have pulmonary arteriovenous malformations (AVM) and there is usually a family history of AVM in these patients. The malformations are usually located in the lower lobes. In this paper, I describe a 49‐year‐old male patient with dyspnoea, cough, haemoptysis and epistaxis. Physical examination showed nasal telangiectasias, cyanosis of the lips and nails, and a systolic bruit over the left lung. Chest X‐ray revealed a 5‐cm mass in the left lower lobe and after magnetic resonance examination, together with 3‐D magnetic resonance angiography, it was demonstrated to be a pulmonary arteriovenous fistula. The history of a niece with a similiar history of suspected pulmonary arteriovenous fistula led me to consider the possibility of Rendu–Osler–Weber syndrome presenting with a pulmonary arteriovenous fistula.